MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'PPAR Research' source. Sun, 21 Mar 2010 17:01:12 +0100 http://www.medworm.com/index.php?rid=3373631&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F427401.html Neuroepithelial tumors represent a heterogeneous class of human tumors including benignant and malignant tumors. The incidence of central nervous system neoplasms ranges from 3.8 to 5.1 cases per 100,000 in the population. Among malignant neuroepithelial tumors, with regard to PPAR ligands, the most extensively studied were tumors of astrocytic origin and neuroblastoma. PPARs are expressed in developing and adult neuroepithelial cells, even if with different localization and relative abundance. The majority of malignant neuroepithelial tumors have poor prognosis and do not respond to conventional therapeutic protocols, therefore, new therapeutic approaches are needed. Natural and synthetic PPAR ligands may represent a starting point for the formulation of new therapeutic approaches to be u... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3373631 Wed, 17 Mar 2010 16:29:51 +0100 3373631 http://www.medworm.com/index.php?rid=3369671&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F952734.html Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria β-oxidation with an increase in both peroxisomal β-oxidation, and microsomal ω-oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARα activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid β-oxidation an... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3369671 Tue, 16 Mar 2010 17:42:35 +0100 3369671 http://www.medworm.com/index.php?rid=3349712&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F438673.html PPARγ ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN) PPARγ mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs). In quiescent CASMCs, adenovirus-expressed DN-PPARγ promoted G1→S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARγ expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7. Conversely, overexpression of wild-type (WT) or constitutively-active (CA) PPARγ inhibited cell cycle progression and the activity and exp... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3349712 Wed, 10 Mar 2010 17:48:02 +0100 3349712 http://www.medworm.com/index.php?rid=3317955&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F867678.html Tumor suppressor candidate 5 (TUSC5) is a gene expressed abundantly in white adipose tissue (WAT), brown adipose tissue (BAT), and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ) agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs) in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitaz... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3317955 Mon, 01 Mar 2010 17:12:20 +0100 3317955 http://www.medworm.com/index.php?rid=3315911&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F814609.html The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combine... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3315911 Sun, 28 Feb 2010 16:02:30 +0100 3315911 http://www.medworm.com/index.php?rid=3297799&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F818945.html PPARγ activation in type 2 diabetic patients results in a marked improvement in insulin and glucose parameters, resulting from an improvement of whole-body insulin sensitivity. Adipose tissue is the major mediator of PPARγ action on insulin sensitivity. PPARγ activation in mature adipocytes induces the expression of a number of genes involved in the insulin signaling cascade, thereby improving insulin sensitivity. PPARγ is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPARγ plays an important role in regulating lipid, metabolism in mature adipocytes by increasing fatty acid trapping. Finally, adipose tissue produces several cytokines that regul... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3297799 Tue, 23 Feb 2010 16:37:51 +0100 3297799 http://www.medworm.com/index.php?rid=3275353&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F956427.html Osteosarcoma (OS) is the most common nonhematologic malignancy of bone in children and adults. Although dysregulation of tumor suppressor genes and oncogenes, such as Rb, p53, and the genes critical to cell cycle control, genetic stability, and apoptosis have been identified in OS, consensus genetic changes that lead to OS development are poorly understood. Disruption of the osteogenic differentiation pathway may be at least in part responsible for OS tumorigenesis. Current OS management involves chemotherapy and surgery. Peroxisome proliferator-activated receptor (PPAR) agonists and/or retinoids can inhibit OS proliferation and induce apoptosis and may inhibit OS growth by promoting osteoblastic terminal differentiation. Thus, safe and effective PPAR agonists and/or retinoid derivatives c... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3275353 Tue, 16 Feb 2010 16:14:38 +0100 3275353 http://www.medworm.com/index.php?rid=3110651&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F785369.html Peroxisome proliferator activated receptor γ (PPARγ) agonists are widely used in the treatment of type 2 diabetes. Side effects of drug treatment include both fluid retention and a lowering of blood pressure. Data from animal and human studies suggest that these effects arise, at least in part, from drug-induced changes in the kidney. In order to capitalize on the positive aspect (lowering of blood pressure) and exclude the negative one (fluid retention), it is necessary to understand the mechanisms of action underlying each of the effects. When interpreted with known physiological principles, current hypotheses regarding potential mechanisms produce enigmas that are difficult to resolve. This paper is a summary of the current understanding of PPARγ agonist effects on ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3110651 Tue, 22 Dec 2009 15:53:30 +0100 3110651 http://www.medworm.com/index.php?rid=3106605&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F925309.html The PPARs are integral parts of the RXR-dependent signaling networks. Many other nuclear receptor subfamily 1 members also require RXR as their obligatory heterodimerization partner and they are often co-expressed in any given tissue. Therefore, the PPARs often complete with other RXR-dependent nuclear receptors and this competition has important biological implications. Thorough understanding of this cross-talk at the molecular level is crucial to determine the detailed functional roles of the PPARs. At the level of DNA binding, most RXR heterodimers bind selectively to the well-known “DR1 to 5” DNA response elements. As a result, many heterodimers share the same DR element and must complete with each other for DNA binding. At the level of heterodimerization, the partners of R... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3106605 Sun, 20 Dec 2009 15:47:44 +0100 3106605 http://www.medworm.com/index.php?rid=3043943&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F543746.html In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=3043943 Tue, 01 Dec 2009 18:31:14 +0100 3043943 http://www.medworm.com/index.php?rid=3043942&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F189091.html (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=3043942 Tue, 01 Dec 2009 18:31:14 +0100 3043942 http://www.medworm.com/index.php?rid=3018557&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F193413.html This study investigated the role of the 5′-UTR in regulating the efficiency with which the message is translated to protein. A coupled in vitro transcription-translation assay demonstrated that PPAR-γ1, -γ2, and -γ5 are efficiently translated, whereas PPAR-γ4 and -γ7 are poorly translated. An in vivo reporter gene assay using each 5′-UTR upstream of the firefly luciferase gene showed that the 5′-UTRs for PPAR-γ1, -γ2, and -γ4 enhanced translation, whereas the 5′-UTRs for PPAR-γ5 and -γ7 inhibited translation. Models of RNA secondary structure, obtained by the mfold software, were used to explain the mechanism of regulation by each 5′-UTR. In general, it was found that the translational ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3018557 Mon, 23 Nov 2009 15:55:48 +0100 3018557 http://www.medworm.com/index.php?rid=3016892&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F528327.html The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in irradiation toxicity, and the possibility of using their ligands for radioprotection. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=3016892 Sun, 22 Nov 2009 15:51:04 +0100 3016892 http://www.medworm.com/index.php?rid=3003195&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F801609.html PPARα is a lipid-activable transcription factor that mediates the adaptive response to fasting. Recent data indicate an important role of brain PPARα in physiological functions. However, it has not yet been shown whether PPARα in brain can be activated in the fasting state. Here we demonstrate that fasting of rats increased mRNA concentrations of typical PPARα target genes implicated in β-oxidation of fatty acids (acyl-CoA oxidase, carnitine palmitoyltransferase-1, medium chain acyl-CoA dehydrogenase) and ketogenesis (mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase) in pituitary gland and partially also in frontal cortex and diencephalon compared to nonfasted animals. These data strongly indicate that fasting activates PPARα in brain and... PPAR Research journals http://www.medworm.com/rss/comments.php?id=3003195 Wed, 18 Nov 2009 16:13:15 +0100 3003195 http://www.medworm.com/index.php?rid=2995266&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F530265.html This study was performed to determine the effects of GA on total PPARγ and LPL expression levels, lipid parameters and HOMA-IR. Oral administration of 100 mg/kg GA for 24 hours resulted in an increase in insulin sensitivity with decreases in blood glucose, serum insulin and HOMA-IR. Improvement in serum lipid parameters was also observed with a decrease in triacylglycerol, total cholesterol and LDL-cholesterol and an elevation in HDL-cholesterol. GA administration also resulted in up-regulation of total PPARγ and LPL expression levels in the visceral and subcutaneous adipose tissues, abdominal and quadriceps femoris muscles, as well as liver and kidney, with a significant up-regulation only in the visceral adipose tissue, abdominal and quadriceps femoris muscles.... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2995266 Mon, 16 Nov 2009 16:13:14 +0100 2995266 http://www.medworm.com/index.php?rid=2926786&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F476217.html Preclinical studies to predict the efficacy and safety of drugs have conventionally been conducted almost exclusively in mice and rats as rodents, despite the differences in drug metabolism between humans and rodents. Furthermore, human (h) viruses such as hepatitis viruses do not infect the rodent liver. A mouse bearing a liver in which the hepatocytes have been largely repopulated with h-hepatocytes would overcome some of these disadvantages. We have established a practical, efficient, and large-scale production system for such mice. Accumulated evidence has demonstrated that these hepatocyte-humanized mice are a useful and reliable animal model, exhibiting h-type responses in a series of in vivo drug processing (adsorption, distribution, metabolism, excretion) experiments and in the inf... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2926786 Mon, 26 Oct 2009 16:26:31 +0100 2926786 http://www.medworm.com/index.php?rid=2926785&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F816957.html Numerous studies have indicated that PPARγ plays multiple roles such as in inflammation, cell cycle control, cell proliferation, apoptosis, and carcinogenesis, thus PPARγ contributes to the homeostasis. Many in vitro studies have showed that ligand-induced activation of PPARγ possess antitumor effect in many cancers including CRC. However, the role of PPARγ in gastrointestinal cancers, especially in colorectal cancer, is rather controversial. Nevertheless, some recent studies with the positive results on the possible application of PPARγ ligands, such as Bezafibrate or Rosiglitazone in gastrointestinal cancers, have suggested a potential usefulness of PPARγ agonists in cancer prevention and therapy. In this review, the authors discuss the recent de... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2926785 Mon, 26 Oct 2009 16:26:31 +0100 2926785 http://www.medworm.com/index.php?rid=2924702&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F874126.html In conclusion, the p.P12A variant of the PPARγ2 may influence cardiovascular risk through effects on lipid metabolism in obese T2D Palestinian patients. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2924702 Sun, 25 Oct 2009 15:41:00 +0100 2924702 http://www.medworm.com/index.php?rid=2902725&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F729876.html Nuclear hormone receptors, including RXR and PPARγ, represent novel therapeutic targets in melanoma. We have previously shown that the DRO subline of the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD) treatment in vitro and in vivo. We performed microarray analysis of A375(DRO) after TZD and combination rexinoid/TZD treatment in which the calcium binding protein S100A2 had increased expression after rexinoid or TZD treatment and a synergistic increase to combination treatment. Increased S100A2 expression is dependent on an intact PPARγ receptor, but it is not sufficient to mediate the antiproliferative effects of rexinoid/TZD treatment. Over expression of S100A2 enhanced the effect of rexinoid and TZD treatment while inhibition of S100A2 expression ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2902725 Sun, 18 Oct 2009 14:34:27 +0100 2902725 http://www.medworm.com/index.php?rid=2803430&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F234975.html Whole-brain irradiation (WBI) represents the primary mode of treatment for brain metastases; about 200 000 patients receive WBI each year in the USA. Up to 50% of adult and 100% of pediatric brain cancer patients who survive >6 months post-WBI will suffer from a progressive, cognitive impairment. At present, there are no proven long-term treatments or preventive strategies for this significant radiation-induced late effect. Recent studies suggest that the pathogenesis of radiation-induced brain injury involves WBI-mediated increases in oxidative stress and/or inflammatory responses in the brain. Therefore, anti-inflammatory strategies can be employed to modulate radiation-induced brain injury. Peroxisomal proliferator-activated receptors (PPARs) are ligand-activated tra... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2803430 Thu, 17 Sep 2009 17:47:43 +0100 2803430 http://www.medworm.com/index.php?rid=2792732&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F748174.html In conclusion, RXR and PPAR play a central role in the onset and perpetuation of the mechanisms underling all steps of the clinical progression in ALD. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2792732 Mon, 14 Sep 2009 17:52:08 +0100 2792732 http://www.medworm.com/index.php?rid=2757069&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F861238.html Virtual screening (VS) is a discovery technique to identify novel compounds with therapeutic and preventive efficacy against disease. Our current focus is on the in silico screening and discovery of novel peroxisome proliferator-activated receptor-gamma (PPARγ) agonists. It is well recognized that PPARγ agonists have therapeutic applications as insulin sensitizers in type 2 diabetes or as anti-inflammatories. VS is a cost- and time-effective means for identifying small molecules that have therapeutic potential. Our long-term goal is to devise computational approaches for testing the PPARγ-binding activity of extensive naturally occurring compound libraries prior to testing agonist activity using ligand-binding and reporter assays. This review summarizes the high potent... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2757069 Wed, 02 Sep 2009 17:52:13 +0100 2757069 http://www.medworm.com/index.php?rid=2711610&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F460764.html Cardiovascular disease is a major cause of morbidity and mortality among people with type 2 diabetes mellitus. The peroxisome proliferator-activated receptor (PPAR) agonists have a significant role on glucose and fat metabolism. Thiazolidinediones (TZDs) are predominantly PPARγ agonists, and their primary benefit appears to be the prevention of diabetic complications by improving glycemic control and lipid profile. Recently, the cardiovascular safety of rosiglitazone was brought to center stage following meta analyses and the interim analysis of the RECORD trial. Current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. This review article discusses the mechanism of action of PPAR agonists and correlates i... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2711610 Wed, 19 Aug 2009 11:33:09 +0100 2711610 http://www.medworm.com/index.php?rid=2688032&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F728941.html During phase II metabolism, a substrate is rendered more hydrophilic through the covalent attachment of an endogenous molecule. The cytosolic sulfotransferase (SULT) and UDP-glucuronosyltransferase (UGT) families of enzymes account for the majority of phase II metabolism in humans and animals. In general, phase II metabolism is considered to be a detoxication process, as sulfate and glucuronide conjugates are more amenable to excretion and elimination than are the parent substrates. However, certain products of phase II metabolism (e.g., unstable sulfate conjugates) are genotoxic. Members of the nuclear receptor superfamily are particularly important regulators of SULT and UGT gene transcription. In metabolically active tissues, increasing evidence supports a major role for lipid-sensing t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2688032 Tue, 11 Aug 2009 12:02:56 +0100 2688032 http://www.medworm.com/index.php?rid=2678172&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F345320.html Breast cancer is the most prominent cancer among females in the United States. There are a number of risk factors associated with development of breast cancer, including consumption of a high-fat diet and obesity. Plasminogen activator inhibitor-1 (PAI-1) is a cytokine upregulated in obesity whose expression is correlated with a poor prognosis in breast cancer. As a key mediator of adipogenesis and regulator of adipokine production, peroxisome proliferator-activated receptor-γ (PPAR-γ) is involved in PAI-1 expression from adipose tissue. We summarize the current knowledge linking PPAR-γ and PAI-1 expression to high-fat diet and obesity in the risk of breast cancer. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2678172 Fri, 07 Aug 2009 12:12:16 +0100 2678172 http://www.medworm.com/index.php?rid=2653191&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F543584.html (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2653191 Thu, 30 Jul 2009 12:18:57 +0100 2653191 http://www.medworm.com/index.php?rid=2616482&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2010%2F848645.html Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n=3448) from 47 organs including skin neoplasms (n=323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2616482 Mon, 20 Jul 2009 12:01:36 +0100 2616482 http://www.medworm.com/index.php?rid=2597622&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F393408.html (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2597622 Tue, 14 Jul 2009 12:05:03 +0100 2597622 http://www.medworm.com/index.php?rid=2597621&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F501739.html Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ) regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and i... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2597621 Tue, 14 Jul 2009 12:05:03 +0100 2597621 http://www.medworm.com/index.php?rid=2575879&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F101857.abs.html Peroxisome proliferator-activated receptor gamma (PPARγ) activation decreased serum testosterone (T) in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2) in female rats. This implies modulation of female sex steroid hormones by PPARγ. It is not clear if PPARγ modulates sex steroid hormones in diabetic males. Because PPARγ activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPARγ activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPARγ activation on serum and intratesticular T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and E2 concentrations in male ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2575879 Tue, 07 Jul 2009 12:02:00 +0100 2575879 http://www.medworm.com/index.php?rid=2575878&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F237865.abs.html In conclusion, chronic PPAR-γ therapy may predispose the cardiorenal system to a potential sequela of structural and/or functional changes that may be deleterious with regard to morbidity and mortality. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2575878 Tue, 07 Jul 2009 12:02:00 +0100 2575878 http://www.medworm.com/index.php?rid=2575877&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F571365.abs.html The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγ is a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγ agonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγ an... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2575877 Tue, 07 Jul 2009 12:02:00 +0100 2575877 http://www.medworm.com/index.php?rid=2575876&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F830501.html It is now well established that the development and progression of a variety of human malignancies are associated with dysregulated activity of the insulin-like growth factor (IGF) system. In this regard, promising drugs have been developed to target the IGF-I receptor or its ligands. These therapies are limited by the development of insulin resistance and compensatory hyperinsulinemia, which in turn, may stimulate cancer growth. Novel therapeutic approaches are, therefore, required. Synthetic PPAR-γ agonists, such as thiazolidinediones (TZDs), are drugs universally used as antidiabetic agents in patients with type 2 diabetes. In addition of acting as insulin sensitizers, PPAR-γ agonists mediate in vitro and in vivo pleiotropic anticancer effects. At least some of these effec... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2575876 Tue, 07 Jul 2009 12:02:00 +0100 2575876 http://www.medworm.com/index.php?rid=2552472&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F350351.html (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2552472 Mon, 29 Jun 2009 16:33:07 +0100 2552472 http://www.medworm.com/index.php?rid=2552471&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F571365.html The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγ is a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγ agonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγ an... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2552471 Mon, 29 Jun 2009 16:33:07 +0100 2552471 http://www.medworm.com/index.php?rid=2503857&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F101857.html Peroxisome proliferator-activated receptor gamma (PPARγ) activation decreased serum testosterone (T) in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2) in female rats. This implies modulation of female sex steroid hormones by PPARγ. It is not clear if PPARγ modulates sex steroid hormones in diabetic males. Because PPARγ activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPARγ activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPARγ activation on serum and intratesticular T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and E2 concentrations in male ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2503857 Thu, 25 Jun 2009 08:48:30 +0100 2503857 http://www.medworm.com/index.php?rid=2503856&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F237865.html In conclusion, chronic PPAR-γ therapy may predispose the cardiorenal system to a potential sequela of structural and/or functional changes that may be deleterious with regard to morbidity and mortality. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2503856 Thu, 25 Jun 2009 08:48:30 +0100 2503856 http://www.medworm.com/index.php?rid=2467981&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F548178.html Conclusions. Rosiglitazone reduces chronic inflammatory responses and improves levels of markers of endothelial dysfunction in patients with diabetes and CAD. PPAR-γ agonist may have a beneficial effect on the vascular endothelium through its anti-inflammatory mechanism and may be useful as therapy in patients undergoing PCI. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467981 Wed, 10 Jun 2009 03:19:57 +0100 2467981 http://www.medworm.com/index.php?rid=2467980&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F134059.html Lipid mediators can trigger physiological responses by activating nuclear hormone receptors, such as the peroxisome proliferator-activated receptors (PPARs). PPARs, in turn, control the expression of networks of genes encoding proteins involved in all aspects of lipid metabolism. In addition, PPARs are tumor growth modifiers, via the regulation of cancer cell apoptosis, proliferation, and differentiation, and through their action on the tumor cell environment, namely, angiogenesis, inflammation, and immune cell functions. Epidemiological studies have established that tumor progression may be exacerbated by chronic inflammation. Here, we describe the production of the lipids that act as activators of PPARs, and we review the roles of these receptors in inflammation and cancer. Finally, we c... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467980 Wed, 10 Jun 2009 03:19:57 +0100 2467980 http://www.medworm.com/index.php?rid=2467979&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F316306.html Statins increase peroxisome proliferator-activated receptor α (PPARα) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin-induced HNF-4α. (2) PPARα mRNA expression was increased by statin... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467979 Wed, 10 Jun 2009 03:19:57 +0100 2467979 http://www.medworm.com/index.php?rid=2467978&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F507141.html Lipodystrophy and metabolic alterations are major complications of antiretroviral therapy in HIV-infected patients. In vitro studies using cultured murine and human adipocytes revealed that some protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were implicated to a different extent in adipose cell dysfunction and that a chronic incubation with some PIs decreased mRNA and protein expression of PPARγ. Defective lamin A maturation linked to PI inhibitory activity could impede the nuclear translocation of SREBP1c, therefore, reducing PPARγ expression. Adipose cell function was partially restored by the PPARγ agonists, thiazolidinediones. Adverse effects of PIs and NRTIs have also been reported in macrophages, a cell type that coexists with, ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467978 Wed, 10 Jun 2009 03:19:57 +0100 2467978 http://www.medworm.com/index.php?rid=2467977&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F483485.html Insulin resistance and type 2 diabetes are associated with hepatitis C virus infection. A wealth of clinical and experimental data suggests that the virus is directly interfering with the insulin signalling in hepatocytes. In the case of at least one viral genotype (the type 3a), insulin resistance seems to be directly mediated by the downregulation of the peroxisome proliferator-activated receptor γ. Whether and how this interaction may be manipulated pharmacologically, in order to improve the responsiveness to antivirals of insulin resistant chronic hepatitis C, patients remain to be fully explored. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467977 Wed, 10 Jun 2009 03:19:57 +0100 2467977 http://www.medworm.com/index.php?rid=2467976&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F164163.html Peroxisome proliferator-activated receptors belong to the superfamily of ligand-dependent nuclear receptor transcription factors, which include three subtypes: PPAR-α, β/δ, and γ. PPAR-δ, play important roles in the regulation of cell growth and differentiation as well as tissue wound and repair. Emerging evidence has also demonstrated that PPAR-δ is implicated in lipids and glucose metabolism. Most recently, the direct effects of PPAR-δ on cardiovascular processes such as endothelial function and angiogenesis have also been investigated. Therefore, it is suggested that PPAR-δ may have critical roles in cardiovascular pathophysiology and is a potential target for therapeutic intervention of cardiovascular disorders such as atheroscler... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467976 Wed, 10 Jun 2009 03:19:57 +0100 2467976 http://www.medworm.com/index.php?rid=2467975&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F827096.html Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPARγ pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPARγ agonist activity in addition to its effects ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467975 Wed, 10 Jun 2009 03:19:57 +0100 2467975 http://www.medworm.com/index.php?rid=2467974&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F103167.html Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists) have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exa... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467974 Wed, 10 Jun 2009 03:19:57 +0100 2467974 http://www.medworm.com/index.php?rid=2467973&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F286249.html In this review, the role of NF-κB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-κB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-α (PPARα) activation in non-hepatic tissues can lead to the inhibition of NF-κB activation. Several lines of evidence support the hypothesis that the activation of NF-κB by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-κB in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-κB knockout models. Specifically, the induction of cell proliferation and th... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467973 Wed, 10 Jun 2009 03:19:57 +0100 2467973 http://www.medworm.com/index.php?rid=2467972&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F786781.html A major genomic region involved in Wegener's granulomatosis includes the gene for retinoid receptor beta (RXRB) which forms heterodimers with peroxisome proliferator-activated receptors (PPARs). It is unclear whether this association directly arises from the RXRB allele(s) or via a linked variation. In order to reveal any hitherto unknown and potentially disease-relevant variation of the RXRB gene, we have genotyped four tagging SNPs of this genomic region and have directly sequenced selected WG patients and controls representing disease-associated haplotypes. Additionally, we have genotyped 2 SNPs each in the genes for PPARα and PPARγ (PPARA and PPARG). Hence, we confirmed the strong association of the RXRB locus with WG but could not reveal any novel variation in RXRB. ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467972 Wed, 10 Jun 2009 03:19:57 +0100 2467972 http://www.medworm.com/index.php?rid=2467971&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F369602.html Omega-3 fatty acids (FAs) have the potential to regulate gene expression via the peroxisome proliferator-activated receptor α (PPARα); therefore, genetic variations in this gene may impact its transcriptional activity on target genes. It is hypothesized that the transcriptional activity by wild-type L162-PPARα is enhanced to a greater extent than the mutated variant (V162-PPARα) in the presence of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or a mixture of EPA:DHA. To examine the functional difference of the two allelic variants on receptor activity, transient co-transfections were performed in human hepatoma HepG2 cells activated with EPA, DHA and EPA:DHA mixtures. Results indicate that the addition of EPA or DHA demonstrate pote... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467971 Wed, 10 Jun 2009 03:19:57 +0100 2467971 http://www.medworm.com/index.php?rid=2467970&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F635680.html Renal endothelial damage is pivotal in the initiation and progression of renal disease. Damaged renal endothelium may be regenerated through proliferation of local endothelium and circulation-derived endothelial progenitor cells. Activation of the PPAR-γ-receptors present on endothelial cells affects their cellular behavior. Proliferation, apoptosis, migration, and angiogenesis by endothelial cells are modulated, but may involve both stimulation and inhibition depending on the specific circumstances. PPAR-γ-receptor activation stimulates the production of nitric oxide, C-type natriuretic peptide, and superoxide dismutase, while endothelin-1 production is inhibited. Together, they augment endothelial function, resulting in blood pressure lowering and direct renoprotective effe... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467970 Wed, 10 Jun 2009 03:19:57 +0100 2467970 http://www.medworm.com/index.php?rid=2467969&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F706283.html The collecting duct (CD) expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth bu... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467969 Wed, 10 Jun 2009 03:19:57 +0100 2467969 http://www.medworm.com/index.php?rid=2467968&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F750238.html Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA) metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPARγ. Targeting LOX/COX enzymes and inducing activation of PPARγ have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation o... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467968 Wed, 10 Jun 2009 03:19:57 +0100 2467968 http://www.medworm.com/index.php?rid=2467967&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F879523.html Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467967 Wed, 10 Jun 2009 03:19:57 +0100 2467967 http://www.medworm.com/index.php?rid=2467966&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F183108.html Involvement of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in kidney physiology has been explored recently. Synthetic PPARγ ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli. Activation of PPARγ has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis. Beside many beneficial effects, PPARγ activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy. This unwanted effect is due to the activation of PPAR&#x03... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467966 Wed, 10 Jun 2009 03:19:57 +0100 2467966 http://www.medworm.com/index.php?rid=2467965&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F745821.html Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARα and PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARα and PPARγ anti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδ in cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδ selective synthetic agonists were found, improving studies about the physiological and pathophysiological ro... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467965 Wed, 10 Jun 2009 03:19:57 +0100 2467965 http://www.medworm.com/index.php?rid=2467964&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F421376.html Currently infection with the human immunodeficiency virus-1 (HIV-1) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy (ART). However, chronic use of ART has been associated with a number of toxicities; including significant reductions in bone mineral density (BMD) and disorders of the fat metabolism. The peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor is vital for the development and maintenance of mature and developing adipocytes. Alterations in PPARγ expression have been implicated as a factor in the mechanism of HIV-1-associated lipodystrophy. Both reduced BMD and lipodystrophy have been well described as complications of HIV-1 infection and treatment, and a question remains as to their interdepe... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467964 Wed, 10 Jun 2009 03:19:57 +0100 2467964 http://www.medworm.com/index.php?rid=2467963&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F786359.html (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467963 Wed, 10 Jun 2009 03:19:57 +0100 2467963 http://www.medworm.com/index.php?rid=2467962&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F357204.html The topic of peroxisome proliferator-activated receptors has been developed in the field of hepatology allowing envisaging therapeutic strategies for the most frequent chronic liver diseases such as chronic infection with hepatitis C virus (HCV). PPARs contribute to wide physiological processes within the liver such as lipid/glucid metabolisms, inflammatory response, cell differentiation, and cell cycle. In vitro experiments and animal studies showed that PPARα discloses anti-inflammatory property, and PPARγ discloses anti-inflammatory, antifibrogenic, and antiproliferative properties in the liver. Experimental and human studies showed impaired PPARs expression and function during HCV infection. The available nonhepatotoxic agonists of PPARs may constitute a progress in the t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467962 Wed, 10 Jun 2009 03:19:57 +0100 2467962 http://www.medworm.com/index.php?rid=2467961&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F649286.html The Diabetes Control and Complications Trial (DCCT) involved intensive diabetes therapy of subjects with type 1 diabetes mellitus (T1DM) for an average period of 6.5 years. A subset of these subjects gained excessive weight. We tested for association of polymorphisms in 8 candidate genes with the above trait. We found the Gly482Ser polymorphism in the peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) to be significantly associated with weight gain in males (P=.0045) but not in females. The Ser allele was associated with greater weight gain than the Gly allele (P=.005). Subjects with a family history of type 2 diabetes mellitus (T2DM) were more common among those who gained excessive weight. We conclude that T2DM and the Gly482Ser polymorphism in PGC1&... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467961 Wed, 10 Jun 2009 03:19:57 +0100 2467961 http://www.medworm.com/index.php?rid=2467960&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2008%2F736362.html (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467960 Wed, 10 Jun 2009 03:19:57 +0100 2467960 http://www.medworm.com/index.php?rid=2467959&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F145124.html Thirty years after its discovery, the hepatitis B virus (HBV) still remains a major global public health problem. Worldwide, two billion subjects have been infected, 350 million have a chronic infection and more than 600 000 die annually of HBV-related liver disease or hepatocellular carcinoma; new infections occur because of the presence of a large reservoir of chronic carriers of the virus. Since a decade several studies describe the interrelations between HBV and nuclear receptors and more particularly the peroxisome proliferator-activated receptors (PPARs). After a brief introduction, this review will make a rapid description of HBV incidence and biology. Then a report of the literature on the role of PPARs on viral transcription and replication will be developed. Finally, the r... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467959 Wed, 10 Jun 2009 03:19:57 +0100 2467959 http://www.medworm.com/index.php?rid=2467958&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F906167.html Due to the introduction of active HIV antiretroviral treatment, AIDS-related morbidity and mortality have markedly decreased and liver diseases are now a major cause of morbidity and mortality in HIV-infected patients. Chronic liver injury encompasses a wide spectrum of diseases due to HCV and HBV coinfection, drug-related toxicity, and NASH. HIV-infected patients who are receiving treatment present with a high prevalence of metabolic complications and lipodystrophy. Those patients are at high risk of nonalcoholic fatty liver disease, the liver feature of the metabolic syndrome. This review will focus on (1) the liver injuries in HIV-infected patients; (2) both the current experimental and human data regarding PPAR and liver diseases; (3) the interactions between HIV and PPAR; (4) the pot... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467958 Wed, 10 Jun 2009 03:19:57 +0100 2467958 http://www.medworm.com/index.php?rid=2467957&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F849538.html The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interac... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467957 Wed, 10 Jun 2009 03:19:57 +0100 2467957 http://www.medworm.com/index.php?rid=2467956&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F498352.html Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD) or Ulcerative Colitis (UC) have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferati... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467956 Wed, 10 Jun 2009 03:19:57 +0100 2467956 http://www.medworm.com/index.php?rid=2467955&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F706852.html MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-γ agonist that lowers glucose in the absence of some of the side effects, such as weight gain and edema, that are observed with the TZDs. Interestingly MBX-102 also displays pronounced triglyceride lowering in preclinical rodent models and in humans. Although in vitro reporter gene studies indicated that MBX-102 acid is a highly selective PPAR-γ agonist that lacks PPAR-α activity, we sought to determine if PPAR-α activation in vivo could possibly contribute to the triglyceride lowering abilities of MBX-102. In vivo studies using ZDF and ZF rats demonstrated that MBX-102 lowered plasma triglycerides. However in ZF rats, MBX-102 had no effect on liver weight or on hepatic expression levels of PPAR-&#x03B1... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467955 Wed, 10 Jun 2009 03:19:57 +0100 2467955 http://www.medworm.com/index.php?rid=2467954&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F425289.html The aim of the present study was to examine whether endocannabinoids cause PPARγ-mediated vascular actions. Functional vascular studies were carried out in rat aortae. Anandamide and N-arachidonoyl-dopamine (NADA), but not palmitoylethanolamide, caused significant vasorelaxation over time (2 hours). Vasorelaxation to NADA, but not anandamide, was inhibited by CB1 receptor antagonism (AM251, 1 μM), and vasorelaxation to both anandamide and NADA was inhibited by PPARγ antagonism (GW9662, 1 μM). Pharmacological inhibition of de novo protein synthesis, nitric oxide synthase, and super oxide dismutase abolished the responses to anandamide and NADA. Removal of the endothelium partly inhibited the vasorelaxant responses to anandamide and NADA. Inhibition... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467954 Wed, 10 Jun 2009 03:19:57 +0100 2467954 http://www.medworm.com/index.php?rid=2467953&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F853707.html Acute attacks of multiple sclerosis (MS) are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA) is now known to involve induction of indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10), where IL-10 requires subsequent heme oxygenase-1 (HMOX-1) induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2) can prevent demyelination in experimental autoimmune encephalomyelitis (EAE) animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating an... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467953 Wed, 10 Jun 2009 03:19:57 +0100 2467953 http://www.medworm.com/index.php?rid=2467952&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fppar%2F2009%2F412949.html In nature, hibernating animals encounter fasting, cold temperature and short day seasonally. Torpor is a state of decreased physiological activity in an animal, usually characterized by a reduced body temperature and rate of metabolism to adapt such a severe environment. Ablation of the central clock synchronizer, the suprachiasmatic nucleus in brain, abolishes torpor, a hibernation-like state, implicating the circadian clock involved in this seasonal change. Biologists knows well the energy source of daily heterotherms/hibernators changed from glucose to lipids in winter. Here we review several lines of evidence of a master transcriptional regulator in lipid catabolism, PPARα, in the control of torpor through FGF21-NPY pathway. This indicate the importance of circadian—and ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2467952 Wed, 10 Jun 2009 03:19:57 +0100 2467952 http://www.medworm.com/index.php?rid=2462741&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F412949 In nature, hibernating animals encounter fasting, cold temperature and short day seasonally. Torpor is a state of decreased physiological activity in an animal, usually characterized by a reduced body temperature and rate of metabolism to adapt such a severe environment. Ablation of the central clock synchronizer, the suprachiasmatic nucleus in brain, abolishes torpor, a hibernation-like state, implicating the circadian clock involved in this seasonal change. Biologists knows well the energy source of daily heterotherms/hibernators changed from glucose to lipids in winter. Here we review several lines of evidence of a master transcriptional regulator in lipid catabolism, PPARα, in the control of torpor through FGF21-NPY pathway. This indicate the importance of circadian—and ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2462741 Mon, 08 Jun 2009 07:04:22 +0100 2462741 http://www.medworm.com/index.php?rid=2422737&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F853707 Acute attacks of multiple sclerosis (MS) are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA) is now known to involve induction of indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10), where IL-10 requires subsequent heme oxygenase-1 (HMOX-1) induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2) can prevent demyelination in experimental autoimmune encephalomyelitis (EAE) animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating an... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2422737 Wed, 20 May 2009 05:12:29 +0100 2422737 http://www.medworm.com/index.php?rid=2380057&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F425289 The aim of the present study was to examine whether endocannabinoids cause PPARγ-mediated vascular actions. Functional vascular studies were carried out in rat aortae. Anandamide and N-arachidonoyl-dopamine (NADA), but not palmitoylethanolamide, caused significant vasorelaxation over time (2 hours). Vasorelaxation to NADA, but not anandamide, was inhibited by CB1 receptor antagonism (AM251, 1 μM), and vasorelaxation to both anandamide and NADA was inhibited by PPARγ antagonism (GW9662, 1 μM). Pharmacological inhibition of de novo protein synthesis, nitric oxide synthase, and super oxide dismutase abolished the responses to anandamide and NADA. Removal of the endothelium partly inhibited the vasorelaxant responses to anandamide and NADA. Inhibition... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2380057 Thu, 30 Apr 2009 19:14:16 +0100 2380057 http://www.medworm.com/index.php?rid=2363719&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F706852 MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-γ agonist that lowers glucose in the absence of some of the side effects, such as weight gain and edema, that are observed with the TZDs. Interestingly MBX-102 also displays pronounced triglyceride lowering in preclinical rodent models and in humans. Although in vitro reporter gene studies indicated that MBX-102 acid is a highly selective PPAR-γ agonist that lacks PPAR-α activity, we sought to determine if PPAR-α activation in vivo could possibly contribute to the triglyceride lowering abilities of MBX-102. In vivo studies using ZDF and ZF rats demonstrated that MBX-102 lowered plasma triglycerides. However in ZF rats, MBX-102 had no effect on liver weight or on hepatic expression levels of PPAR-&#x03B1... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2363719 Fri, 24 Apr 2009 18:43:05 +0100 2363719 http://www.medworm.com/index.php?rid=2356205&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F498352 Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD) or Ulcerative Colitis (UC) have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferati... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2356205 Wed, 22 Apr 2009 14:49:15 +0100 2356205 http://www.medworm.com/index.php?rid=2340007&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F906167 Due to the introduction of active HIV antiretroviral treatment, AIDS-related morbidity and mortality have markedly decreased and liver diseases are now a major cause of morbidity and mortality in HIV-infected patients. Chronic liver injury encompasses a wide spectrum of diseases due to HCV and HBV coinfection, drug-related toxicity, and NASH. HIV-infected patients who are receiving treatment present with a high prevalence of metabolic complications and lipodystrophy. Those patients are at high risk of nonalcoholic fatty liver disease, the liver feature of the metabolic syndrome. This review will focus on (1) the liver injuries in HIV-infected patients; (2) both the current experimental and human data regarding PPAR and liver diseases; (3) the interactions between HIV and PPAR; (4) the pot... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2340007 Sat, 18 Apr 2009 18:26:40 +0100 2340007 http://www.medworm.com/index.php?rid=2340006&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F849538 The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interac... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2340006 Sat, 18 Apr 2009 18:26:40 +0100 2340006 http://www.medworm.com/index.php?rid=2324083&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F357204 The topic of peroxisome proliferator-activated receptors has been developed in the field of hepatology allowing envisaging therapeutic strategies for the most frequent chronic liver diseases such as chronic infection with hepatitis C virus (HCV). PPARs contribute to wide physiological processes within the liver such as lipid/glucid metabolisms, inflammatory response, cell differentiation, and cell cycle. In vitro experiments and animal studies showed that PPARα discloses anti-inflammatory property, and PPARγ discloses anti-inflammatory, antifibrogenic, and antiproliferative properties in the liver. Experimental and human studies showed impaired PPARs expression and function during HCV infection. The available nonhepatotoxic agonists of PPARs may constitute a progress in the t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2324083 Sat, 11 Apr 2009 17:50:22 +0100 2324083 http://www.medworm.com/index.php?rid=2324082&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F649286 The Diabetes Control and Complications Trial (DCCT) involved intensive diabetes therapy of subjects with type 1 diabetes mellitus (T1DM) for an average period of 6.5 years. A subset of these subjects gained excessive weight. We tested for association of polymorphisms in 8 candidate genes with the above trait. We found the Gly482Ser polymorphism in the peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) to be significantly associated with weight gain in males (P=.0045) but not in females. The Ser allele was associated with greater weight gain than the Gly allele (P=.005). Subjects with a family history of type 2 diabetes mellitus (T2DM) were more common among those who gained excessive weight. We conclude that T2DM and the Gly482Ser polymorphism in PGC1&... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2324082 Sat, 11 Apr 2009 17:50:22 +0100 2324082 http://www.medworm.com/index.php?rid=2324081&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F736362 (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2324081 Sat, 11 Apr 2009 17:50:22 +0100 2324081 http://www.medworm.com/index.php?rid=2324080&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F145124 Thirty years after its discovery, the hepatitis B virus (HBV) still remains a major global public health problem. Worldwide, two billion subjects have been infected, 350 million have a chronic infection and more than 600 000 die annually of HBV-related liver disease or hepatocellular carcinoma; new infections occur because of the presence of a large reservoir of chronic carriers of the virus. Since a decade several studies describe the interrelations between HBV and nuclear receptors and more particularly the peroxisome proliferator-activated receptors (PPARs). After a brief introduction, this review will make a rapid description of HBV incidence and biology. Then a report of the literature on the role of PPARs on viral transcription and replication will be developed. Finally, the r... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2324080 Sat, 11 Apr 2009 17:50:22 +0100 2324080 http://www.medworm.com/index.php?rid=2295284&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F745821 Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARα and PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARα and PPARγ anti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδ in cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδ selective synthetic agonists were found, improving studies about the physiological and pathophysiological ro... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2295284 Sun, 29 Mar 2009 01:00:08 +0100 2295284 http://www.medworm.com/index.php?rid=2295283&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F421376 Currently infection with the human immunodeficiency virus-1 (HIV-1) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy (ART). However, chronic use of ART has been associated with a number of toxicities; including significant reductions in bone mineral density (BMD) and disorders of the fat metabolism. The peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor is vital for the development and maintenance of mature and developing adipocytes. Alterations in PPARγ expression have been implicated as a factor in the mechanism of HIV-1-associated lipodystrophy. Both reduced BMD and lipodystrophy have been well described as complications of HIV-1 infection and treatment, and a question remains as to their interdepe... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2295283 Sun, 29 Mar 2009 01:00:08 +0100 2295283 http://www.medworm.com/index.php?rid=2295282&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F786359 (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2295282 Sun, 29 Mar 2009 01:00:08 +0100 2295282 http://www.medworm.com/index.php?rid=2257933&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F183108 Involvement of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in kidney physiology has been explored recently. Synthetic PPARγ ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli. Activation of PPARγ has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis. Beside many beneficial effects, PPARγ activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy. This unwanted effect is due to the activation of PPAR&#x03... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2257933 Fri, 13 Mar 2009 05:35:22 +0100 2257933 http://www.medworm.com/index.php?rid=2234785&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F706283 The collecting duct (CD) expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth bu... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2234785 Thu, 05 Mar 2009 10:13:16 +0100 2234785 http://www.medworm.com/index.php?rid=2234783&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F750238 Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA) metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPARγ. Targeting LOX/COX enzymes and inducing activation of PPARγ have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation o... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2234783 Thu, 05 Mar 2009 10:13:16 +0100 2234783 http://www.medworm.com/index.php?rid=2234781&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F879523 Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2234781 Thu, 05 Mar 2009 10:13:16 +0100 2234781 http://www.medworm.com/index.php?rid=2218035&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F369602 Omega-3 fatty acids (FAs) have the potential to regulate gene expression via the peroxisome proliferator-activated receptor α (PPARα); therefore, genetic variations in this gene may impact its transcriptional activity on target genes. It is hypothesized that the transcriptional activity by wild-type L162-PPARα is enhanced to a greater extent than the mutated variant (V162-PPARα) in the presence of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or a mixture of EPA:DHA. To examine the functional difference of the two allelic variants on receptor activity, transient co-transfections were performed in human hepatoma HepG2 cells activated with EPA, DHA and EPA:DHA mixtures. Results indicate that the addition of EPA or DHA demonstrate pote... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2218035 Fri, 27 Feb 2009 04:50:03 +0100 2218035 http://www.medworm.com/index.php?rid=2218034&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F635680 Renal endothelial damage is pivotal in the initiation and progression of renal disease. Damaged renal endothelium may be regenerated through proliferation of local endothelium and circulation-derived endothelial progenitor cells. Activation of the PPAR-γ-receptors present on endothelial cells affects their cellular behavior. Proliferation, apoptosis, migration, and angiogenesis by endothelial cells are modulated, but may involve both stimulation and inhibition depending on the specific circumstances. PPAR-γ-receptor activation stimulates the production of nitric oxide, C-type natriuretic peptide, and superoxide dismutase, while endothelin-1 production is inhibited. Together, they augment endothelial function, resulting in blood pressure lowering and direct renoprotective effe... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2218034 Fri, 27 Feb 2009 04:50:03 +0100 2218034 http://www.medworm.com/index.php?rid=2178287&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F786781 A major genomic region involved in Wegener's granulomatosis includes the gene for retinoid receptor beta (RXRB) which forms heterodimers with peroxisome proliferator-activated receptors (PPARs). It is unclear whether this association directly arises from the RXRB allele(s) or via a linked variation. In order to reveal any hitherto unknown and potentially disease-relevant variation of the RXRB gene, we have genotyped four tagging SNPs of this genomic region and have directly sequenced selected WG patients and controls representing disease-associated haplotypes. Additionally, we have genotyped 2 SNPs each in the genes for PPARα and PPARγ (PPARA and PPARG). Hence, we confirmed the strong association of the RXRB locus with WG but could not reveal any novel variation in RXRB. ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2178287 Thu, 12 Feb 2009 03:41:56 +0100 2178287 http://www.medworm.com/index.php?rid=2142072&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F286249 In this review, the role of NF-κB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-κB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-α (PPARα) activation in non-hepatic tissues can lead to the inhibition of NF-κB activation. Several lines of evidence support the hypothesis that the activation of NF-κB by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-κB in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-κB knockout models. Specifically, the induction of cell proliferation and th... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2142072 Thu, 29 Jan 2009 16:22:40 +0100 2142072 http://www.medworm.com/index.php?rid=2138585&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F827096 Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPARγ pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPARγ agonist activity in addition to its effects ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2138585 Wed, 28 Jan 2009 12:42:25 +0100 2138585 http://www.medworm.com/index.php?rid=2138584&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F103167 Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists) have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exa... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2138584 Wed, 28 Jan 2009 12:42:25 +0100 2138584 http://www.medworm.com/index.php?rid=2081664&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F483485 Insulin resistance and type 2 diabetes are associated with hepatitis C virus infection. A wealth of clinical and experimental data suggests that the virus is directly interfering with the insulin signalling in hepatocytes. In the case of at least one viral genotype (the type 3a), insulin resistance seems to be directly mediated by the downregulation of the peroxisome proliferator-activated receptor γ. Whether and how this interaction may be manipulated pharmacologically, in order to improve the responsiveness to antivirals of insulin resistant chronic hepatitis C, patients remain to be fully explored. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2081664 Tue, 06 Jan 2009 12:03:12 +0100 2081664 http://www.medworm.com/index.php?rid=2081663&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F164163 Peroxisome proliferator-activated receptors belong to the superfamily of ligand-dependent nuclear receptor transcription factors, which include three subtypes: PPAR-α, β/δ, and γ. PPAR-δ, play important roles in the regulation of cell growth and differentiation as well as tissue wound and repair. Emerging evidence has also demonstrated that PPAR-δ is implicated in lipids and glucose metabolism. Most recently, the direct effects of PPAR-δ on cardiovascular processes such as endothelial function and angiogenesis have also been investigated. Therefore, it is suggested that PPAR-δ may have critical roles in cardiovascular pathophysiology and is a potential target for therapeutic intervention of cardiovascular disorders such as atheroscler... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2081663 Tue, 06 Jan 2009 12:03:12 +0100 2081663 http://www.medworm.com/index.php?rid=2075959&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F507141 Lipodystrophy and metabolic alterations are major complications of antiretroviral therapy in HIV-infected patients. In vitro studies using cultured murine and human adipocytes revealed that some protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were implicated to a different extent in adipose cell dysfunction and that a chronic incubation with some PIs decreased mRNA and protein expression of PPARγ. Defective lamin A maturation linked to PI inhibitory activity could impede the nuclear translocation of SREBP1c, therefore, reducing PPARγ expression. Adipose cell function was partially restored by the PPARγ agonists, thiazolidinediones. Adverse effects of PIs and NRTIs have also been reported in macrophages, a cell type that coexists with, ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2075959 Sat, 03 Jan 2009 17:25:18 +0100 2075959 http://www.medworm.com/index.php?rid=2062431&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F316306 Statins increase peroxisome proliferator-activated receptor α (PPARα) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin-induced HNF-4α. (2) PPARα mRNA expression was increased by statin... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2062431 Wed, 24 Dec 2008 16:39:42 +0100 2062431 http://www.medworm.com/index.php?rid=2056649&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F134059 Lipid mediators can trigger physiological responses by activating nuclear hormone receptors, such as the peroxisome proliferator-activated receptors (PPARs). PPARs, in turn, control the expression of networks of genes encoding proteins involved in all aspects of lipid metabolism. In addition, PPARs are tumor growth modifiers, via the regulation of cancer cell apoptosis, proliferation, and differentiation, and through their action on the tumor cell environment, namely, angiogenesis, inflammation, and immune cell functions. Epidemiological studies have established that tumor progression may be exacerbated by chronic inflammation. Here, we describe the production of the lipids that act as activators of PPARs, and we review the roles of these receptors in inflammation and cancer. Finally, we c... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2056649 Mon, 22 Dec 2008 12:54:14 +0100 2056649 http://www.medworm.com/index.php?rid=2048434&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F159415 The role of PPARγ in adipocyte differentiation has fueled intense interest in the function of this steroid nuclear receptor for regulation of malignant cell growth and differentiation. Given the antiproliferative and differentiating effects of PPARγ ligands on liposarcoma cells, investigation of PPARγ expression and ligand activation in other solid tumors such as breast, colon, and prostate cancers ensued. The anticancer effects of PPARγ ligands in cell culture and rodent models of a multitude of tumor types suggest broad applicability of these agents to cancer therapy. This review focuses on the clinical use of PPARγ ligands, specifically the thiazolidinediones, for the treatment and prevention of cancer. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2048434 Thu, 18 Dec 2008 15:54:58 +0100 2048434 http://www.medworm.com/index.php?rid=2048433&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F746935 Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors (NRs) that regulate genes involved in lipid and glucose metabolism. PPAR activity is regulated by interactions with cofactors and of interest are cofactors with ubiquitin ligase activity. The E6-associated protein (E6-AP) is an E3 ubiquitin ligase that affects the activity of other NRs, although its effects on PPARs have not been examined. E6-AP inhibited the ligand-independent transcriptional activity of PPARα and PPARβ, with marginal effects on PPARγ, and decreased basal mRNA levels of PPARα target genes. Inhibition of PPARα activity required the ubiquitin ligase function of E6-AP, but occurred in a proteasome-independent manner. PPARα interacted with E6-AP, and in mice tre... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2048433 Thu, 18 Dec 2008 15:54:58 +0100 2048433 http://www.medworm.com/index.php?rid=2048432&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F548178 Conclusions. Rosiglitazone reduces chronic inflammatory responses and improves levels of markers of endothelial dysfunction in patients with diabetes and CAD. PPAR-γ agonist may have a beneficial effect on the vascular endothelium through its anti-inflammatory mechanism and may be useful as therapy in patients undergoing PCI. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=2048432 Thu, 18 Dec 2008 15:54:58 +0100 2048432 http://www.medworm.com/index.php?rid=2041401&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F794814 Peroxisome proliferator-activated receptor δ (PPARδ, also known as PPARβ) has ubiquitous distribution and extensive biological functions. The reproductive function of PPARδ was first revealed in the uterus at the implantation site. Since then, PPARδ and its ligand have been discovered in all reproductive tissues, including the gametes and the preimplantation embryos. PPARδ in preimplantation embryos is normally activated by oviduct-derived PPARδ ligand. PPARδ activation is associated with an increase in embryonic cell proliferation and a decrease in programmed cell death (apoptosis). On the other hand, the role of PPARδ and its ligand in gamete formation and function is less well understood. This review will summarize the repro... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2041401 Wed, 17 Dec 2008 15:42:02 +0100 2041401 http://www.medworm.com/index.php?rid=2036162&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F932632 Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which belongs to the family of nuclear hormone receptors. Recent in vitro studies have shown that PPARγ can regulate the transcription of phosphatase and tensin homolog on chromosome ten (PTEN), a known tumor suppressor. PTEN is a susceptibility gene for a number of disorders, including breast and thyroid cancer. Activation of PPARγ through agonists increases functional PTEN protein levels that subsequently induces apoptosis and inhibits cellular growth, which suggests that PPARγ may be a tumor suppressor. Indeed, several in vivo studies have demonstrated that genetic alterations of PPARγ can promote tumor progression. These results are supported by observ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2036162 Mon, 15 Dec 2008 12:52:15 +0100 2036162 http://www.medworm.com/index.php?rid=2028830&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F581348 Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARγ and α, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) and db/db mice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptors γ and α (PPARγ/α) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARγ and PPAR&#x03... PPAR Research journals http://www.medworm.com/rss/comments.php?id=2028830 Thu, 11 Dec 2008 15:03:13 +0100 2028830 http://www.medworm.com/index.php?rid=1999624&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F373524 Highly active antiretroviral therapy (HAART)-associated metabolic complications include lipoatrophy (loss of subcutaneous adipose tissue (SAT)) and insulin resistance. Thiazolidinediones are insulin-sensitizing antidiabetic agents which—as an untoward side effect in obese diabetic patients—increase SAT. Furthermore, troglitazone has improved lipoatrophy and glycemic control in non-HIV patients with various forms of lipodystrophy. These data have led to 14 clinical trials to examine whether thiazolidinediones could be useful in the treatment of HAART-associated metabolic complications. The results of these studies indicate very modest, if any, effect on lipoatrophic SAT, probably due to ongoing HAART negating the beneficial effect. The benefit might be more prominent in pati... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1999624 Mon, 01 Dec 2008 12:54:01 +0100 1999624 http://www.medworm.com/index.php?rid=1999623&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2009%2F607902 PPARγ is a ligand-dependent master transcription factor controlling adipocyte differentiation as well as multiple biological processes taking place in other cells present in adipose tissue depots such as macrophages. Recent research indicates that HIV-1 infection-related events may alter adipose tissue biology through several mechanisms involving PPARγ, ranging from direct effects of HIV-1-encoded proteins on adipocytes to the promotion of a proinflammatory environment that interferes with PPARγ actions. This effect of HIV-1 on adipose tissue cells can occur even in the absence of direct infection of adipocytes, as soluble HIV-1-encoded proteins such as Vpr may enter cells and inhibit PPARγ action. Moreover, repression of PPARγ actions may relieve inhibit... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1999623 Mon, 01 Dec 2008 12:54:01 +0100 1999623 http://www.medworm.com/index.php?rid=1985663&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F904251 The growth and metastasis of cancers intimately involve the vasculature and in particular the endothelial cell layer. Tumours require new blood vessel formation via angiogenesis to support growth. In addition, inflammation, coagulation, and platelet activation are common signals in the growth and metastasis of tumour cells. The endothelium plays a central role in the homeostatic control of inflammatory cell recruitment, regulating platelet activation and coagulation pathways. PPARα, -β/δ, and -γ are all expressed in endothelial cells. This review will discuss the roles of PPARs in endothelial cells in relation to angiogenesis, inflammation, coagulation, and platelet control pathways. In particular, we will discuss the recent evidence that supports the hypothesis... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1985663 Tue, 25 Nov 2008 13:34:34 +0100 1985663 http://www.medworm.com/index.php?rid=1970122&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F945275 PPARγ is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPARγ has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPARγ role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPARγ image as potential anticancer drug. Currently PPARγ is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, ho... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1970122 Wed, 19 Nov 2008 13:40:51 +0100 1970122 http://www.medworm.com/index.php?rid=1945630&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F293538 Peroxisome proliferator-activated receptor (PPAR) α ligands (Wy-14,643, and fenofibrate) and PPARγ ligands (troglitazone and ciglitazone) inhibit antigen-induced cysteinyl leukotriene production in immunoglobulin E-treated mast cells. The inhibitory effect of these ligands on cysteinyl leukotriene production is quite strong and is almost equivalent to that of the anti-asthma compound zileuton. To develop new aspects for anti-asthma drugs the pharmacological target of these compounds should be clarified. Experiments with bone-marrow-derived mast cells from PPARα knockout mice and pharmacological inhibitors of PPARγ suggest that the inhibitory effects of these ligands are independent of PPARs α and γ. The mechanisms of the PPAR-independent inhibition... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1945630 Sun, 09 Nov 2008 15:33:25 +0100 1945630 http://www.medworm.com/index.php?rid=1945629&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F780452 peroxisome proliferator-activated receptors (PPARs) are nuclear receptors acting as lipid sensors. Besides its metabolic activity in peripheral organs, the PPAR beta/delta isotype is highly expressed in the brain and its deletion in mice induces a brain developmental defect. Nevertheless, exploration of PPARβ action in the central nervous system remains sketchy. The lipid content alteration observed in PPARβ null brains and the positive action of PPARβ agonists on oligodendrocyte differentiation, a process characterized by lipid accumulation, suggest that PPARβ acts on the fatty acids and/or cholesterol metabolisms in the brain. PPARβ could also regulate central inflammation and antioxidant mechanisms in the damaged brain. Even if not fully understood, th... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1945629 Sun, 09 Nov 2008 15:33:25 +0100 1945629 http://www.medworm.com/index.php?rid=1934794&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F473804 Dendritic cells (DCs) can regulate all elements of the immune system, and therefore are an ideal target for vaccination. During the last two decades, as a result of extensive research, DCs became the primary target of antitumor vaccination as well. A critical issue of antitumor vaccination is the phenotype of the dendritic cell used. It has been recently shown that several nuclear hormone receptors, and amongst them the lipid-activated nuclear receptor and peroxisome proliferator-activated receptor gamma (PPARγ), have important roles in effecting the immunophenotype of human dendritic cells. It regulates primarily lipid metabolism and via this it influences the immunophenotype of DCs by altering lipid antigen uptake, presentation, and also other immune functions. In this review, we ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1934794 Wed, 05 Nov 2008 19:32:11 +0100 1934794 http://www.medworm.com/index.php?rid=1915512&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F125387 The prevalence of obesity in the USA and worldwide has reached epidemic proportions during the last two decades. Drugs currently available for the treatment of obesity provide no more than 5% placebo-adjusted weight loss and are associated with undesirable side effects. Peroxisome proliferator-activated receptor (PPAR) modulators offer potential benefits for the treatment of obesity and its associated complications but their development has been complicated by biological, technical, and regulatory challenges. Despite significant challenges, PPAR modulators are attractive targets for the treatment of obesity and could offer a viable alternative to the millions of patients who fail to lose weight following rigorous dieting and exercise protocols. In addition, PPAR modulators have the pot... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1915512 Wed, 29 Oct 2008 16:14:29 +0100 1915512 http://www.medworm.com/index.php?rid=1915511&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F672829 Thyroid cancer is uncommon and exhibits relatively low mortality rates. However, a subset of patients experience inexorable growth, metastatic spread, and mortality. Unfortunately, for these patients, there have been few significant advances in treatment during the last 50 years. While substantial advances have been made in recent years about the molecular genetic events underlying papillary thyroid cancer, the more aggressive follicular thyroid cancer remains poorly understood. The recent discovery of the PAX8/PPARγ translocation in follicular thyroid carcinoma has promoted progress in the role of PPARγ as a tumor suppressor and potential therapeutic target. The PAX8/PPARγ fusion gene appears to be an oncogene. It is most often expressed in follicular carcinomas and e... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1915511 Wed, 29 Oct 2008 16:14:29 +0100 1915511 http://www.medworm.com/index.php?rid=1813087&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F172676 The peroxisome proliferator-activated receptors (PPARs), which are ligand-inducible transcription factors expressed in a variety of tissues, have been shown to perform key roles in lipid homeostasis. In physiological situations such as fasting and physical exercise, one PPAR subtype, PPARδ, triggers a transcriptional program in skeletal muscle leading to a switch in fuel usage from glucose/fatty acids to solely fatty acids, thereby drastically increasing its oxidative capacity. The metabolic action of PPARδ has also been verified in humans. In addition, it has become clear that the action of PPARδ is not restricted to skeletal muscle. Indeed, PPARδ has been shown to play a crucial role in whole-body lipid homeostasis as well as in insulin sensitivity, and it is active n... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1813087 Mon, 22 Sep 2008 16:49:43 +0100 1813087 http://www.medworm.com/index.php?rid=1795201&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F614852 Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a ligand-activated transcription factor with essential functions in the regulation of lipid catabolism, glucose homeostasis, and inflammation, which makes it a potentially relevant drug target for the treatment of major human diseases. In addition, there is strong evidence that PPARβ/δ modulates oncogenic signaling pathways and tumor growth. Consistent with these observations, numerous reports have clearly documented a role for PPARβ/δ in cell cycle control, differentiation, and apoptosis. However, the precise role of PPARβ/δ in tumorigenesis and cell proliferation remains controversial. This review summarizes our current knowledge and proposes a model corrobora... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1795201 Tue, 16 Sep 2008 15:14:04 +0100 1795201 http://www.medworm.com/index.php?rid=1791952&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F649808 Although thiazolidinediones (TZDs) were found to be ligands for peroxisome proliferators-activated receptorγ (PPARγ), the mechanism by which TZDs exert their anticancer effect remains unclear. Furthermore, the effect of TZDs on metastatic and angiogenesis potential of cancer cells is unknown. Our results in this paper show that rosiglitazone inhibited SGC-7901 gastric cancer cells growth, caused G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. The effects of rosiglitazone on SGC-7901 cancer cells were completely reversed by treatment with PPARγ antagonist GW9662. Rosiglitazone inhibited SGC-7901 cell migration, invasiveness, and the expression of MMP-2 in dose-dependent manner via PPARγ-independent manner. Rosiglitazone reduced the VEGF induced... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1791952 Mon, 15 Sep 2008 14:35:51 +0100 1791952 http://www.medworm.com/index.php?rid=1790762&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F465715 Drug binding to plasma proteins restricts their free and active concentrations, thereby affecting their pharmacokinetic properties. Species differences in plasma protein levels complicate the understanding of interspecies pharmacodynamic and toxicological effects. MBX-102 acid/JNJ39659100 is a novel PPAR-γ agonist in development for the treatment of type 2 diabetes. Studies were performed to evaluate plasma protein binding to MBX-102 acid and evaluate species differences in free drug levels. Equilibrium dialysis studies demonstrated that MBX-102 acid is highly bound (>98%) to human, rat and mouse albumin and that free MBX-102 acid levels are higher in rodent than in human plasma. Interspecies differences in free drug levels were further studied using PPAR-γ tran... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1790762 Sun, 14 Sep 2008 14:06:06 +0100 1790762 http://www.medworm.com/index.php?rid=1790761&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F513943 Today, there is increasing evidence that PPARγ agonists, including thiazolidinediones (TDZs) and nonthiazolidinediones, block the motility and invasiveness of glioma cells and other highly migratory tumor entities. However, the mechanism(s) by which PPARγ activators mediate their antimigratory and anti-invasive properties remains elusive. This letter gives a short review on the debate and adds to the current knowledge by applying a PPARγ inactive derivative of the TDZ troglitazone (Rezulin) which potently counteracts experimental glioma progression in a PPARγ independent manner. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1790761 Sun, 14 Sep 2008 14:06:06 +0100 1790761 http://www.medworm.com/index.php?rid=1773519&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F209629 The role of PPARγ in tumorigenesis is controversial. In this article, we review and analyze literature from the past decade that highlights the potential proneoplastic activity of PPARγ. We discuss the following five aspects of the nuclear hormone receptor and its agonists: (1) relative expression of PPARγ in human tumor versus normal tissues; (2) receptor-dependent proneoplastic effects; (3) impact of PPARγ and its agonists on tumors in animal models; (4) clinical trials of thiazolidinediones (TZDs) in human malignancies; (5) TZDs as chemopreventive agents in epidemiology studies. The focus is placed on the most relevant in vivo animal models and human data. In vitro cell line studies are included only when the effects are shown to be dependent on the PPAR&#x03... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1773519 Mon, 08 Sep 2008 13:38:40 +0100 1773519 http://www.medworm.com/index.php?rid=1773518&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F297893 Over the past two years, evidence has emerged that the currently available thiazolidinediones (TZDs), rosiglitazone, and pioglitazone have negative skeletal consequences, at least in women, which are clinically important. Increased fracture risk in women, but not men, was reported for both TZDs, based on analyses of adverse event reports from clinical trials. In short-term clinical trials in women, both TZDs caused more rapid bone loss. In these trials, changes in bone turnover markers suggest a pattern of reduced bone formation without a change in resorption. Although limited, these results support the hypothesis based on rodent and in vitro models that reduced bone formation resulting from activation of peroxisome proliferator-activated receptor-γ (PPARγ) is a central mechani... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1773518 Mon, 08 Sep 2008 13:38:40 +0100 1773518 http://www.medworm.com/index.php?rid=1770863&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F943614 Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor subtype γ (PPARγ) activators that are clinically used as an insulin sensitizer for glycemic control in patients with type 2 diabetes. Additionally, TZDs exhibit novel anti-inflammatory, antioxidant, and antiproliferative properties, indicating therapeutic potential for a wide variety of diseases associated with diabetes and other conditions. The clinical applications of TZDs are limited by the common major side effect of fluid retention. A better understanding of the molecular mechanism of TZD-induced fluid retention is essential for the development of novel therapies with improved safety profiles. An important breakthrough in the field is the finding that the renal collecting duct is a major site for in... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1770863 Sun, 07 Sep 2008 14:15:43 +0100 1770863 http://www.medworm.com/index.php?rid=1755677&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F436489 Peroxisome proliferator-activated receptor-gamma (PPARγ), one of three ligand-activated transcription factors named PPAR, has been identified as a molecular target for cancer chemopreventive agents. PPARγ was initially understood as a regulator of adipocyte differentiation and glucose homeostasis while later on, it became evident that it is also involved in cell differentiation, apoptosis, and angiogenesis, biological processes which are deregulated in cancer. It is now established that PPARγ ligands can induce cell differentiation and yield early antineoplastic effects in several tumor types. Moreover, several bioactive natural products with cancer protecting potential are shown to operate through activation of PPARγ. Overall, PPARγ appears to be a preva... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1755677 Wed, 03 Sep 2008 14:00:49 +0100 1755677 http://www.medworm.com/index.php?rid=1750842&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F759716 Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer and a potentially nongenotoxic carcinogen. Its mechanism had been earlier proposed based on peroxisome proliferator-activated receptor α (PPARα) because metabolites of DEHP are agonists. However, recent evidence also suggests the involvement of non-PPARα multiple pathway in DEHP-induced carcinogenesis. Since there are differences in the function and constitutive expression of PPARα among rodents and humans, species differences are also thought to exist in the carcinogenesis. However, species differences were also seen in the lipase activity involved in the first step of the DEHP metabolism, which should be considered in DEHP-induced carcinogenesis. Taken together, it is very difficult to extrapolate t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1750842 Tue, 02 Sep 2008 14:01:09 +0100 1750842 http://www.medworm.com/index.php?rid=1750841&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F769413 Chemokines are peptide mediators involved in normal development, hematopoietic and immune regulation, wound healing, and inflammation. Among the chemokines is CXCL12, which binds principally to its receptor CXCR4 and regulates leukocyte precursor homing to bone marrow and other sites. This role of CXCL12/CXCR4 is “commandeered” by cancer cells to facilitate the spread of CXCR4-bearing tumor cells to tissues with high CXCL12 concentrations. High CXCR4 expression by cancer cells predisposes to aggressive spread and metastasis and ultimately to poor patient outcomes. As well as being useful as a marker for disease progression, CXCR4 is a potential target for anticancer therapies. It is possible to interfere directly with the CXCL12:CXCR4 axis using peptide or small-molecular-weigh... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1750841 Tue, 02 Sep 2008 14:01:09 +0100 1750841 http://www.medworm.com/index.php?rid=1750840&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F494161 PPARγ is a therapeutic target that has been exploited for treatment of type II diabetes mellitus (T2DM) with agonist drugs. Since PPARγ is expressed by many hematopoietic, mesodermal and epithelial cancers, agonist drugs were tested and shown to have both preclinical and clinical anticancer activities. While preclinical activity has been observed in many cancer types, clinical activity has been observed only in pilot and phase II trials in liposarcoma and prostate cancer. Most studies address agonist compounds, with substantially fewer reports on anticancer effects of PPARγ antagonists. In cancer model systems, some effects of PPARγ agonists were not inhibited by PPARγ antagonists, suggesting noncanonical or PPARγ-independent mechanisms. In additio... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1750840 Tue, 02 Sep 2008 14:01:09 +0100 1750840 http://www.medworm.com/index.php?rid=1734748&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F936906 INT131 (formerly T0903131, T131, AMG131) is a potent non-thiazolidinedione (TZD) selective peroxisome proliferator-activated receptor γ modulator (SPPARM) currently in Phase 2 clinical trials for treatment of type-2 diabetes mellitus (T2DM). This new chemical entity represents a second generation SPPARM approach developed after the first generation PPARγ full agonists to address their inherent limitations. INT131 was specifically and carefully designed using preclinical models to exhibit a biological profile of strong efficacy with de minimis side effects compared to PPARγ full agonists. As a potent PPARγ modulator, INT131 binds to PPARγ with high affinity. In pharmacology models of diabetes and in early clinical studies, it achieved a high level of ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1734748 Wed, 27 Aug 2008 14:46:49 +0100 1734748 http://www.medworm.com/index.php?rid=1734747&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F358052 Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γ and, due to the effects of PPARγ on cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal models. In vitro studies have shown that omega-3 PUFAs inhibit cell proliferation and induce apoptosis in cancer cells through various pathways but one of which involves PPARγ activation. The differential activation of PPARγ and PPARγ-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relat... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1734747 Wed, 27 Aug 2008 14:46:49 +0100 1734747 http://www.medworm.com/index.php?rid=1734746&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F790568 This article summarizes recent research on the relationship between (PPARγ), TZDs, and the COX-2/PGE2 pathways in lung cancer. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1734746 Wed, 27 Aug 2008 14:46:49 +0100 1734746 http://www.medworm.com/index.php?rid=1720943&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F651419 The objective of this study was to investigate the in vivo interaction between DES-activated ERα and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Transcripts for PPARs α, β, and γ and γ1a splice variant were detected in Sprague-Dawley normal rat penis with PPARγ predominating. In addition, PPARγ1b and PPARγ2 were newly induced by DES. The PPARγ transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPARγ protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ERα and induced adipocyte differentiation in ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1720943 Thu, 21 Aug 2008 15:08:58 +0100 1720943 http://www.medworm.com/index.php?rid=1720942&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F520465 Peroxisome proliferator-activated receptors (PPARs) play an important role in regulating both glucose and lipid metabolism. Agonists for both PPARγ and PPARγ have been used to treat dyslipidemia and hyperglycemia, respectively. In addition to affecting glucose metabolism, PPARγ agonists also regulate lipid metabolism. In this review, we will focus on the randomized clinical trials that directly compared the lipid effects of the thiazolidinedione class of PPARγ agonists, pioglitazone and rosiglitazone, head-to-head either as monotherapy or in combination with other lipid-altering or glucose-lowering agents (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1720942 Thu, 21 Aug 2008 15:08:58 +0100 1720942 http://www.medworm.com/index.php?rid=1720941&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F285842 Inflammation has been recognized as an important hallmark of atherosclerosis. The pharmacological activation of PPAR-γ by the thiazolidinediones in diabetes, and of PPAR-α by the fibrates in hyperlipidemia has been shown to help to reduce inflammatory markers in preclinical and clinical studies. PPARs are known to modulate immune pathways through at least three different mechanisms: by direct binding to PPRE of anti-inflammatory cytokines genes; by transrepression of transcription factors like NF-κB and AP-1; or by corepression. The regulation of the inflammatory pathways by PPARs can be achieved on each one of the cells involved in the atherosclerotic process, that is, monocytes, macrophages, T cells, endothelial cells, and smooth muscle cells. Moreover, as eac... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1720941 Thu, 21 Aug 2008 15:08:58 +0100 1720941 http://www.medworm.com/index.php?rid=1710417&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F250568 Induction of differentiation and apoptosis in cancer cells by ligands of PPARγ is a novel therapeutic approach to malignant tumors. Chondrosarcoma (malignant cartilage tumor) and OUMS-27 cells (cell line established from grade III human chondrosarcoma) express PPARγ. PPARγ ligands inhibited cell proliferation in a dose-dependent manner, and induced apoptosis of OUMS-27. The higher-grade chondrosarcoma expressed a higher amount of antiapoptotic Bcl-xL in vivo. The treatment of OUMS-27 by 15d-PGJ2, the most potent endogenous ligand for PPARγ, downregulated expression of Bcl-xL and induced transient upregulation of proapoptotic Bax, which could accelerate cytochrome c release from mitochondria to the cytosol, followed by induction of caspase-dependent apoptosis. 15... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1710417 Sun, 17 Aug 2008 14:43:04 +0100 1710417 http://www.medworm.com/index.php?rid=1705366&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F906542 Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members—PPARα, PPARδ, and PPARγ—that differ in their cell and tissue distribution as well as in their target genes. PPARα is abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPARα, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1705366 Thu, 14 Aug 2008 17:58:52 +0100 1705366 http://www.medworm.com/index.php?rid=1705365&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F204514 The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS). The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CN... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1705365 Thu, 14 Aug 2008 17:58:52 +0100 1705365 http://www.medworm.com/index.php?rid=1701916&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F254108 Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights into the cellular mechanisms involved in the control of energy homeostasis, the regulation of cell differentiation, proliferation, and apoptosis, and the modulation of important biological and pathological processes related to inflammation and cancer biology, among others. Since then, PPARs have become an exciting target for the development of therapies directed at many disorders including cancer. PPARs are expressed in many tumors including lung cancer, and their function has been linked to the process of carcinogenesis. Consequently, intense research is being conducted in this area with the hop... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1701916 Wed, 13 Aug 2008 15:52:01 +0100 1701916 http://www.medworm.com/index.php?rid=1677637&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F638356 (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1677637 Mon, 04 Aug 2008 14:37:41 +0100 1677637 http://www.medworm.com/index.php?rid=1658352&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F904041 In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1658352 Mon, 28 Jul 2008 12:56:30 +0100 1658352 http://www.medworm.com/index.php?rid=1658351&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F658520 Central nervous system (CNS) is an immune privileged site, nevertheless inflammation associates with many CNS diseases. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that regulate immune and inflammatory responses. Specific ligands for PPARα, γ, and δ isoforms have proven effective in the animal models of multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, and trauma/stroke, suggesting their use in the treatment of neuroinflammatory diseases. The activation of NF-κB and Jak-Stat signaling pathways and secretion of inflammatory cytokines are critical in the pathogenesis of CNS diseases. Interestingly, PPAR agonists mitigate CNS disease by modulating inflammatory signaling network in immune cells. In t... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1658351 Mon, 28 Jul 2008 12:56:30 +0100 1658351 http://www.medworm.com/index.php?rid=1658350&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F542694 Proline is metabolized by its own specialized enzymes with their own tissue and subcellular localizations and mechanisms of regulation. The central enzyme in this metabolic system is proline oxidase, a flavin adenine dinucleotide-containing enzyme which is tightly bound to mitochondrial inner membranes. The electrons from proline can be used to generate ATP or can directly reduce oxygen to form superoxide. Although proline may be derived from the diet and biosynthesized endogenously, an important source in the microenvironment is from degradation of extracellular matrix by matrix metalloproteinases. Previous studies showed that proline oxidase is a p53-induced gene and its overexpression can initiate proline-dependent apoptosis by both intrinsic and extrinsic pathways. Another important fa... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1658350 Mon, 28 Jul 2008 12:56:30 +0100 1658350 http://www.medworm.com/index.php?rid=1658349&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F352437 A growing body of evidence indicates that PPAR (peroxisome proliferator-activated receptor) α agonists might have therapeutic usefulness in antitumoral therapy by decreasing abnormal cell growth, and reducing tumoral angiogenesis. Most of the anti-inflammatory and antineoplastic properties of PPAR ligands are due to their inhibitory effects on transcription of a variety of genes involved in inflammation, cell growth and angiogenesis. Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) are crucial agents in inflammatory and angiogenic processes. They also have been significantly associated to cell proliferation, tumor growth, and metastasis, promoting tumor-associated angiogenesis. Aberrant expression of VEGF and COX-2 has been observed in a variety of tumor... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1658349 Mon, 28 Jul 2008 12:56:30 +0100 1658349 http://www.medworm.com/index.php?rid=1623295&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F230893 Chemically synthesized ligands for nuclear receptors of the PPAR family modulate a number of physiological functions, particularly insulin resistance in the context of energy homeostasis and the metabolic syndrome. Additionally, these compounds may treat or prevent the development of many secondary consequences of the metabolic syndrome. Many PPAR agonists are also known to influence the proliferation and apoptosis of breast carcinoma cells though the experiments were carried out at suprapharmacological doses of PPAR ligands. It is possible that the breast epithelium of diabetics exposed to PPAR agonists will experience perturbation of the corresponding signaling pathway. Consequently, these patients' lifetime breast carcinoma risks could be modified, as their breast lesion incidence o... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1623295 Tue, 15 Jul 2008 13:44:05 +0100 1623295 http://www.medworm.com/index.php?rid=1618338&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F546753 We describe how PPAR-α regulates differentiation of T cells by transactivation and/or interaction with other transcription factors. Moreover, PPAR-α agonists have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in mice, suggesting that they could provide a therapy for human autoimmune diseases such as multiple sclerosis. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1618338 Mon, 14 Jul 2008 13:41:47 +0100 1618338 http://www.medworm.com/index.php?rid=1618337&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F403896 Peroxisome proliferator-activated receptors (PPARs) are well studied for their peripheral physiological and pathological impact, but they also play an important role for the pathogenesis of various disorders of the central nervous system (CNS) like multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's, and Parkinson's disease. The observation that PPARs are able to suppress the inflammatory response in peripheral macrophages and in several models of human autoimmune diseases lead to the idea that PPARs might be beneficial for CNS disorders possessing an inflammatory component. The neuroinflammatory response during the course of Alzheimer's disease (AD) is triggered by the neurodegeneration and the deposition of the β-amyloid peptide in extracellular plaques. Non... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1618337 Mon, 14 Jul 2008 13:41:47 +0100 1618337 http://www.medworm.com/index.php?rid=1618336&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F256251 Before the discovery of peroxisome proliferator activated receptors (PPARs), it was well known that certain drugs considered as classical PPAR-alpha agonists induced hepatocarcinoma or peroxisome proliferation in rodents. These drugs were derivatives of fibric acid, and they included clofibrate, bezafibrate, and fenofibrate. However, such toxicity has never been observed in human patients treated with these hypolipidemic drugs. Thiazolidinediones are a new class of PPAR activators showing greater specificity for the γ isoform of PPARs. These drugs are used as insulin sensitizers in the treatment of type II diabetes. In addition, they have been shown to induce cell differentiation or apoptosis in various experimental models of cancer. PPAR-α ligands have also been shown to induc... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1618336 Mon, 14 Jul 2008 13:41:47 +0100 1618336 http://www.medworm.com/index.php?rid=1583195&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F587401 Cholangiocarcinoma is a predominantly fatal cancer, which can be difficult to treat. It has been reported that the administration of pioglitazone temporarily improved not only diabetic control, but also bile duct carcinoma-induced cholangiohepatitis. Pioglitazone is considered to have both direct and indirect mechanisms of action on the tumor-related hepatitis. Several molecules induced by thiazolidinedione, including Smad pathway-related molecules, adipokines, and other lipid metabolism-related proteins, may directly or indirectly suppress tumor development and/or tumor-induced cholangiohepatitis. Although the most frequent and critical side effect of thiazolidinedione is drug-induced hepatitis, it can probably be avoided by careful monitoring of serum hepatic enzyme levels. Thiazolidined... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1583195 Mon, 07 Jul 2008 11:50:07 +0100 1583195 http://www.medworm.com/index.php?rid=1582411&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F524671 Peroxisome proliferators-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. The three PPAR isoforms (α, γ and β/δ) have been found to play a pleiotropic role in cell fat metabolism. Furthermore, in recent years, evidence has been found regarding the antiproliferative, proapoptotic, and differentiation-promoting activities displayed by PPAR ligands, particularly by PPARγ ligands. PPAR ligands affect the expression of different growth-related genes through both PPAR-dependent and PPAR-independent mechanisms. Moreover, an interaction between PPAR ligands and other molecules which strengthen the effects of PPAR ligands has been described. Here we review the action of PPAR on the cont... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1582411 Sun, 06 Jul 2008 11:57:39 +0100 1582411 http://www.medworm.com/index.php?rid=1582410&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F148687 Although the highest levels of PPARγ expression in the body have been reported in the gastrointestinal epithelium, little is known about the physiological functions of that receptor in the gut. Moreover, there is considerable controversy concerning the effects of thiazolidinedione PPARγ agonists on the two major diseases of the gastrointestinal track: colorectal cancer and inflammatory bowel disease. We will undertake to review both historical and recently published data with a view toward summarizing what is presently known about the roles of PPARγ in both physiological and pathological processes in the gastrointestinal epithelium. (Source: PPAR Research) PPAR Research journals http://www.medworm.com/rss/comments.php?id=1582410 Sun, 06 Jul 2008 11:57:39 +0100 1582410 http://www.medworm.com/index.php?rid=1564849&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F349185 Accumulation of amyloid-β peptide (Aβ) appears to contribute to the pathogenesis of Alzheimer's disease (AD). Therapeutic hope for the prevention or removal of Aβ deposits has been placed in strategies involving immunization against the Aβ peptide. Initial Aβ immunization studies in animal models of AD showed great promise. However, when this strategy was attempted in human subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is generally believed that this adverse outcome resulted from a T-cell response to Aβ. Specifically, CD4+ Th1 and Th17 cells may contribute to severe CNS inflammation and limit the utility of Aβ immunization in the treatment of AD. Interleukin (IL)-12 and IL-23 play critical roles in the dev... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1564849 Thu, 03 Jul 2008 11:56:39 +0100 1564849 http://www.medworm.com/index.php?rid=1564848&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F326915 In recent years, the study of the peroxisome proliferators activated receptor gamma (PPAR-γ) as a potential target for cancer prevention and therapy has gained a strong interest. However, the overall biological significance of PPAR-γ in cancer development and progression is still controversial. While many reports documented antiproliferative effects in human cancer cell and animal models, several studies demonstrating potential tumor promoting actions of PPAR-γ ligands raised considerable concerns about the role of PPAR-γ in human cancers. Controversy also exists about the role of PPAR-γ in human pancreatic cancers. The current review summarizes the data about PPAR-γ in pancreatic cancer and highlights the biologically relevant interactions between... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1564848 Thu, 03 Jul 2008 11:56:39 +0100 1564848 http://www.medworm.com/index.php?rid=1564847&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F704165 Peroxisome proliferator-activated receptors (PPARs) are ligand binding transcription factors which function in many physiological roles including lipid metabolism, cell growth, differentiation, and apoptosis. PPARs and their ligands have been shown to play a role in cancer. In particular, PPARγ ligands including endogenous prostaglandins and the synthetic thiazolidinediones (TZDs) can induce apoptosis of cancer cells with antitumor activity. Thus, PPARγ ligands have a potential in both chemoprevention and therapy of several types of cancer either as single agents or in combination with other antitumor agents. Accordingly, the involvement of PPARγ and its ligands in regulation of apoptosis of cancer cells have been extensively studied. Depending on cell types or ligands... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1564847 Thu, 03 Jul 2008 11:56:39 +0100 1564847 http://www.medworm.com/index.php?rid=1564846&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F762398 Peroxisome proliferator-activated receptor-γ (PPARγ) and retinoic acid X-receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFβ1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFβ1 gene by PPARγ activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFβ1 by PPARγ activators can be applied for treating TGFβ1-induced pathophysiologic disorders such as cancer metastasis and fibrosis. In this article, we will discuss the opposing effects of TGFβ on tumor growth and metastasis, and address the signaling pathways regulated by PPARγ... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1564846 Thu, 03 Jul 2008 11:56:39 +0100 1564846 http://www.medworm.com/index.php?rid=1564845&cid=s_37048_62_f&fid=37048&url=http%3A%2F%2Fwww.hindawi.com%2FGetArticle.aspx%3Fdoi%3D10.1155%2F2008%2F169414 Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on the activating stimuli, these cells can develop into different subsets: proinflammatory classically activated (M1) or anti-inflammatory alternatively activated (M2) macrophages. The expression of the nuclear peroxisome proliferator-activated receptors (PPARs) is regulated by M1- or M2-inducing stimuli, and these receptors are generally considered to counteract inflammatory M1 macrophages, while actively promoting M2 activation. This is of importance in a tumor context, where M1 are important initiators of inflammation-driven cancers. As a consequence, PPAR agonists are potentially usefull for inhibiting the earl... PPAR Research journals http://www.medworm.com/rss/comments.php?id=1564845 Thu, 03 Jul 2008 11:56:39 +0100 1564845