Progression of chronic kidney disease in familial LCAT deficiency: a follow-up of the Italian cohort [Patient-Oriented and Epidemiological Research]
In conclusion, this study highlights the severe consequences of FLD, underlines the need of correct early diagnosis and referral of patients to specialized centers, and highlights the urgency for effective treatments to prevent or slow renal disease in patients with LCAT deficiency. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Pavanello, C., Ossoli, A., Arca, M., DErasmo, L., Boscutti, G., Gesualdo, L., Lucchi, T., Sampietro, T., Veglia, F., Calabresi, L. Tags: Patient-Oriented and Epidemiological Research Source Type: research

LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients [Research Articles]
Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearanc...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Dargent, A., Pais de Barros, J.-P., Saheb, S., Bittar, R., Le Goff, W., Carrie, A., Gautier, T., Fournel, I., Rerole, A. L., Choubley, H., Masson, D., Lagrost, L., Quenot, J.-P. Tags: Research Articles Source Type: research

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis [Research Articles]
Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specim...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Guo, J., Mei, H., Sheng, Z., Meng, Q., Veniant, M. M., Yin, H. Tags: Research Articles Source Type: research

PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids [Research Articles]
The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local dist...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Kuge, H., Miyamoto, I., Yagyu, K.-i., Honke, K. Tags: Research Articles Source Type: research

Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation [Research Articles]
In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carri...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Vidal, E., Jun, B., Gordon, W. C., Maire, M.-A., Martine, L., Gregoire, S., Khoury, S., Cabaret, S., Berdeaux, O., Acar, N., Bretillon, L., Bazan, N. G. Tags: Research Articles Source Type: research

Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila [Research Articles]
Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing ...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Hood, S. E., Kofler, X. V., Chen, Q., Scott, J., Ortega, J., Lehmann, M. Tags: Research Articles Source Type: research

Identification of unusual phospholipids from bovine heart mitochondria by HPLC-MS/MS [Research Articles]
In this study, we used normal-phase HPLC for ESI-MS/MS analysis of phospholipids from bovine heart mitochondria. Class separation by HPLC eliminates chances for misidentification of isobaric species from different classes of phospholipids. Chromatography yields simple MS/MS spectra without interference from isobaric species, allowing clear identification of peaks corresponding to fragmented ions containing monoacylglycerol backbone derived from losing one acyl chain. Using these fragmented ions, we characterized individual and isomeric species in each class of mitochondrial phospholipids, including unusual species, such as...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Kim, J., Hoppel, C. L. Tags: Research Articles Source Type: research

Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice [Research Articles]
The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis. Using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), we aimed to clarify the role of myeloid-specific AMPK signaling in male and female mice made acutely atherosclerotic by injection of AAV vector encoding a gain-of-function mutant PCSK9 (PCSK9-AAV) and WD feeding. After 6 weeks of WD feeding, mice received a daily injection of either the AMPK activator...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: LeBlond, N. D., Ghorbani, P., ODwyer, C., Ambursley, N., Nunes, J. R. C., Smith, T. K. T., Trzaskalski, N. A., Mulvihill, E. E., Viollet, B., Foretz, M., Fullerton, M. D. Tags: Research Articles Source Type: research

High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site [Research Articles]
This study opens new possibilities to define the pathogenesis of Lp(a)-related diseases and to facilitate the design of specific therapeutic drugs. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Santonastaso, A., Maggi, M., De Jonge, H., Scotti, C. Tags: Research Articles Source Type: research

Depletion of essential isoprenoids and ER stress induction following acute liver-specific deletion of HMG-CoA reductase [Research Articles]
HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: De Giorgi, M., Jarrett, K. E., Burton, J. C., Doerfler, A. M., Hurley, A., Li, A., Hsu, R. H., Furgurson, M., Patel, K. R., Han, J., Borchers, C. H., Lagor, W. R. Tags: Research Articles Source Type: research

Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous [Research Articles]
Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional SREBP pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how sterol regulatory element (Sre)1 promotes the biosynthesis of sterols and carotenoids in X. dendrorhous is unknown. In this work, comparative RNA-sequencing analysis between modified X. dendrorhous strains that have an active Sre1 protein and the WT was performed to identify Sre1-dependent genes. In addit...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Gomez, M., Campusano, S., Gutierrez, M. S., Sepulveda, D., Barahona, S., Baeza, M., Cifuentes, V., Alcaino, J. Tags: Research Articles Source Type: research

A novel phosphoglycerol serine-glycine lipodipeptide of Porphyromonas gingivalis is a TLR2 ligand [Research Articles]
Porphyromonas gingivalis is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue-destructive processes in human periodontitis. Following oral infection with P. gingivalis, the periodontal bone loss in mice is reported to require the engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of P. gingivalis engage human and mouse TLR2, but a novel lipid class reported here is considerably more potent in engaging TLR2 and the heterodimer receptor TLR2/TLR6. The novel lipid class, termed Lipid 1256, consists of a diacylated phosphoglycerol moiety linke...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Nichols, F. C., Clark, R. B., Maciejewski, M. W., Provatas, A. A., Balsbaugh, J. L., Dewhirst, F. E., Smith, M. B., Rahmlow, A. Tags: Research Articles Source Type: research

Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition [Research Articles]
NAFLD is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to NASH remain unclear. This lack of knowledge leads to a decreased ability to find relevant animal models, predict disease progression, or develop clinical treatments. In the current study, we used multiple mouse models of NAFLD, human correlation data, and selective gene overexpression of steroidogenic acute regulatory protein (StarD1) in ...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Kakiyama, G., Marques, D., Martin, R., Takei, H., Rodriguez-Agudo, D., LaSalle, S. A., Hashiguchi, T., Liu, X., Green, R., Erickson, S., Gil, G., Fuchs, M., Suzuki, M., Murai, T., Nittono, H., Hylemon, P. B., Zhou, H., Pandak, W. M. Tags: Research Articles Source Type: research

The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis [Research Articles]
In this study, we used an in vitro macrophage infection model to investigate simvastatin’s anti-tubercular activity by systematically inhibiting each branch of the mevalonate pathway and evaluating the effects of the branch-specific inhibitors on mycobacterial growth. The anti-tubercular activity of simvastatin used at clinically relevant doses specifically targeted the cholesterol biosynthetic branch rather than the prenylation branches of the mevalonate pathway. Using Western blot analysis and AMP/ATP measurements, we found that simvastatin treatment blocked activation of mechanistic target of rapamycin complex 1 (...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Bruiners, N., Dutta, N. K., Guerrini, V., Salamon, H., Yamaguchi, K. D., Karakousis, P. C., Gennaro, M. L. Tags: Research Articles Source Type: research

Stimulation of ABCB4/MDR3 ATPase activity requires an intact phosphatidylcholine lipid [Research Articles]
ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates PC-lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so, ABCB4 provides PC lipids for extraction into bile. PC lipids account for 40% of the entire pool of lipids in the canalicular membrane with an unknown distribution over both leaflets. Extracted PC lipids end up in so-called mixed micelles. Mixed micelles are composed of phospholipids, bile salts, and cholesterol. Ninety to ninety-five percent of t...
Source: The Journal of Lipid Research - December 1, 2020 Category: Lipidology Authors: Prescher, M., Smits, S. H. J., Schmitt, L. Tags: Research Articles Source Type: research