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Fasting Upregulates PPARα Target Genes in Brain and Influences Pituitary Hormone Expression in a PPARα Dependent MannerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pituitar...
Source: PPAR Research - November 18, 2009 Category: Biology Source Type: journals

Effects of Glycyrrhizic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), Lipoprotein Lipase (LPL), Serum Lipid and HOMA-IR in RatsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 qu...
Source: PPAR Research - November 16, 2009 Category: Biology Source Type: journals

A Human Hepatocyte-Bearing Mouse: An Animal Model to Predict Drug Metabolism and Effectiveness in HumansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: PPAR Research - October 26, 2009 Category: Biology Source Type: journals

Current Understanding of the Role of PPARγ in Gastrointestinal CancersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ga...
Source: PPAR Research - October 26, 2009 Category: Biology Source Type: journals

Impact of the Pro12Ala Polymorphism of the PPAR-Gamma 2 Gene on Metabolic and Clinical Characteristics in the Palestinian Type 2 Diabetic PatientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: PPAR Research - October 25, 2009 Category: Biology Source Type: journals

Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: PPAR Research - October 18, 2009 Category: Biology Source Type: journals

Role of PPARs in Radiation-Induced Brain InjuryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Therefo...
Source: PPAR Research - September 17, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptor and Retinoic X Receptor in Alcoholic Liver DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: PPAR Research - September 14, 2009 Category: Biology Source Type: journals

Virtual Screening as a Technique for PPAR Modulator DiscoveryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 activ...
Source: PPAR Research - September 2, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptor Agonists: Do They Increase Cardiovascular Risk?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 gre...
Source: PPAR Research - August 19, 2009 Category: Biology Source Type: journals

Regulation of Sulfotransferase and UDP-Glucuronosyltransferase Gene Expression by the PPARsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 superfamil...
Source: PPAR Research - August 11, 2009 Category: Biology Source Type: journals

Obesity and Breast Cancer: The Roles of Peroxisome Proliferator-Activated Receptor-γ and Plasminogen Activator Inhibitor-1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 expre...
Source: PPAR Research - August 7, 2009 Category: Biology Source Type: journals

PPAR Research: Successful Launching and Promising FutureEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PPAR Research)
Source: PPAR Research - July 30, 2009 Category: Biology Source Type: journals

Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant MelanomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 significan...
Source: PPAR Research - July 20, 2009 Category: Biology Source Type: journals

PPARs in Viral DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PPAR Research)
Source: PPAR Research - July 14, 2009 Category: Biology Source Type: journals

Regulation of Bile Acid and Cholesterol Metabolism by PPARsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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) regul...
Source: PPAR Research - July 14, 2009 Category: Biology Source Type: journals

Activation of PPARγ by Rosiglitazone Does Not Negatively Impact Male Sex Steroid Hormones in Diabetic RatsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 d...
Source: PPAR Research - July 7, 2009 Category: Biology Source Type: journals

Effects of Chronic PPAR-Agonist Treatment on Cardiac Structure and Function, Blood Pressure, and Kidney in Healthy Sprague-Dawley RatsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: PPAR Research - July 7, 2009 Category: Biology Source Type: journals

New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ (PPARγ) Antitumour Activity: Perspectives from the Insulin ReceptorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pro...
Source: PPAR Research - July 7, 2009 Category: Biology Source Type: journals

PPAR-γ Agonists and Their Effects on IGF-I Receptor Signaling: Implications for CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: PPAR Research - July 7, 2009 Category: Biology Source Type: journals

PPARs: A Double-Edged Sword in Cancer Therapy?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PPAR Research)
Source: PPAR Research - June 29, 2009 Category: Biology Source Type: journals

New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ (PPARγ) Antitumour Activity: Perspectives from the Insulin ReceptorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pro...
Source: PPAR Research - June 29, 2009 Category: Biology Source Type: journals

Activation of PPARγ by Rosiglitazone Does Not Negatively Impact Male Sex Steroid Hormones in Diabetic RatsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 d...
Source: PPAR Research - June 25, 2009 Category: Biology Source Type: journals

Effects of Chronic PPAR-Agonist Treatment on Cardiac Structure and Function, Blood Pressure, and Kidney in Healthy Sprague-Dawley RatsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: PPAR Research - June 25, 2009 Category: Biology Source Type: journals

Antidiabetic Rosiglitazone Reduces Soluble Intercellular Adhesion Molecule-1 Level in Type 2 Diabetic Patients with Coronary Artery DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

PPARs Mediate Lipid Signaling in Inflammation and CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 inflamma...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 CellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 trans...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Antiretroviral-Related Adipocyte Dysfunction and Lipodystrophy in HIV-Infected Patients: Alteration of the PPARγ-Dependent PathwaysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 part...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptors and Hepatitis C Virus-Induced Insulin ResistanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

PPAR-δ in Vascular PathophysiologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

The Role of PPARγ Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ AgonistsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 PPAR&...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

The Role of NF-κB in PPARα-Mediated HepatocarcinogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-;...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Genetic Variability of RXRB, PPARA, and PPARG in Wegener's GranulomatosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 fo...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids TreatmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Protective Actions of PPAR-γ Activation in Renal EndotheliumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 superoxi...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

The PPARδ Ligand GW501516 Reduces Growth but Not Apoptosis in Mouse Inner Medullary Collecting Duct CellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 abo...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Combination Therapy of PPARγ Ligands and Inhibitors of Arachidonic Acid in Lung CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 li...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptors in Diabetic NephropathyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 f...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

PPARγ in Kidney Physiology and PathophysiologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, PPAR...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

PPARδ Activity in Cardiovascular Diseases: A Potential Pharmacological TargetEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 endoge...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Is PPARγ a Prospective Player in HIV-1-Associated Bone Disease?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Development of Synthetic Modulators of PPARs: Current Challenges and Future OpportunitiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PPAR Research)
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptors in HCV-Related InfectionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Experiment...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

The Role of the PGC1α Gly482Ser Polymorphism in Weight Gain due to Intensive Diabetes TherapyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptor δ: A Target with a Broad Therapeutic Potential for Drug DiscoveryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PPAR Research)
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Peroxisome Proliferator-Activated Receptors in HBV-Related InfectionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 rap...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

PPAR and Liver Injury in HIV-Infected PatientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 inj...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

PPARγ2Pro12Ala Polymorphism and Human HealthEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 diabe...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals

Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 identifie...
Source: PPAR Research - June 10, 2009 Category: Biology Source Type: journals