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Journal of Lipid Research

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https://www.readbyqxmd.com/read/28928170/effect-of-adding-bezafibrate-to-standard-lipid-lowering-therapy-on-post-fat-load-lipid-levels-in-patients-with-familial-dysbetalipoproteinemia-a-randomized-placebo-controlled-crossover-trial
#1
Charlotte Koopal, A David Marais, Jan Westerink, Yolanda van der Graaf, Frank L J Visseren
Familial dysbetalipoproteinemia (FD) is a genetic disorder associated with impaired postprandial lipid clearance. The effect of adding bezafibrate to standard lipid-lowering therapy on postprandial and fasting lipid levels in patients with FD is unknown. In this randomized, placebo-controlled, double blind, crossover trial, 15 patients with FD received bezafibrate and placebo for 6 weeks in randomized order in addition to standard lipid-lowering therapy (statin, ezetimibe and/or lifestyle). We assessed post-fat load lipids, expressed as (incremental) area under the curve (iAUC and AUC); as well as fasting levels and safety, and found that adding bezafibrate did not reduce post-fat load non-HDL-cholesterol (non-HDL-C) iAUC (1...
September 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28928169/individual-serum-saturated-fatty-acids-and-markers-of-chronic-subclinical-inflammation-the-insulin-resistance-atherosclerosis-study-iras
#2
Ingrid D Santaren, Steven M Watkins, Angela D Liese, Lynne E Wagenknecht, Marian J Rewers, Steven M Haffner, Carlos Lorenzo, Andreas Festa, Richard P Bazinet, Anthony J Hanley
Recent evidence has documented distinct effects of individual saturated fatty acids (SFA) on cardiometabolic outcomes, with potential protective effects from odd- and very long-chain (VLSFA) SFA. Cross-sectional and prospective associations of individual serum SFA (12:0, 14:0, 15:0, 16:0, 18:0, 20:0, 22:0, and total SFA) with proinflammatory biomarkers and adiponectin were investigated in 555 adults from the Insulin Resistance Atherosclerosis Study (IRAS). Principal components (PC) analysis of proinflammatory markers yielded 3 clusters: PC 1: fibrinogen, white cell count, CRP; PC 2: PAI-1, TNF-α; IL-18; PC 3: IL-6, IL-8...
September 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28912302/prevention-of-renal-apob-retention-is-protective-against-diabetic-nephropathy-role-of-tgf-%C3%AE-inhibition
#3
Patricia G Wilson, Joel C Thompson, Meghan H Yoder, Richard Charnigo, Lisa R Tannock
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy. We previously demonstrated that renal lipoproteins co-localize with biglycan, a renal proteoglycan. The purpose of this study was to determine if prevention of renal lipid (apoB) accumulation attenuates diabetic nephropathy. Biglycan deficient and biglycan wildtype Ldlr-/- mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated TGF-b, in some experiments mice were injected with either the TGF-b neutralizing antibody 1D11 or with 13C4, an irrelevant control antibody...
September 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28893842/hdl-structure-and-function-is-profoundly-affected-when-stored-frozen-in-the-absence-of-cryoprotectants
#4
Michael Holzer, Sabine Kern, Markus Trieb, Athina Trakaki, Gunther Marsche
Analysis of structural and functional parameters of HDL have gained significant momentum in recent years since they are stronger predictors of cardiovascular risk than HDL-cholesterol levels. Surprisingly, in most HDL studies very low attention is paid to HDL storage, which might critically affect functional properties. In the present study, we systematically examined the impact of storage and freezing on structural/functional properties of freshly isolated HDL. Initial damage to HDL starts between week one and four of storage...
September 11, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28887372/the-apolipoprotein-c-iii-gln38lys-variant-associated-with-human-hypertriglyceridemia-is-a-gain-of-function-mutation
#5
Meenakshi Sundaram, Kaitlin R Curtis, Mohsen Amir Alipour, Nicholas D LeBlond, Kaitlyn D Margison, Rebecca A Yaworski, Robin J Parks, Adam D McIntyre, Robert A Hegele, Morgan D Fullerton, Zemin Yao
Recent cell culture and animal studies have suggested expression of human apolipoprotein (apo) C-III in the liver has a profound impact on the triacylglycerol (TAG)-rich VLDL1 production under lipid-rich conditions. The apoC-III Gln38Lys variant was identified in subjects of Mexican origin with moderate hypertriglyceridemia. We postulated that Gln38Lys (C3QK), being a gain-of-function mutation, promotes hepatic VLDL1 assembly/secretion. To test this hypothesis, we expressed C3QK in McA-RH7777 cells and apoc3-null mice to contrast its effect with wildtype apoC-III (C3WT)...
September 8, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28874443/amelioration-of-diet-induced-steatohepatitis-in-mice-following-combined-therapy-with-aso-fsp27-and-fenofibrate
#6
Ananthi Rajamoorthi, Noemi Arias, Jeannine Basta, Richard G Lee, Ángel Baldán
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD progresses from benign steatosis to steatohepatitis (NASH) to cirrhosis, and is linked to hepatocellular carcinoma. No targeted treatment is currently approved for NAFLD/NASH. We showed that fat-specific protein 27 (FSP27), a lipid droplet-associated protein that controls triglyceride turnover in the hepatocyte, is required for fasting- and diet-induced triglyceride accumulation in the liver. However, silencing Fsp27 with antisense oligonucleotides (ASOs) did not improve hepatosteatosis in genetic nor nutritional mouse models of obesity...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28874442/use-of-next-generation-sequencing-to-detect-ldlr-gene-copy-number-variation-in-familial-hypercholesterolemia
#7
Michael A Iacocca, Jian Wang, Jacqueline S Dron, John F Robinson, Adam D McIntyre, Henian Cao, Robert A Hegele
Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the LDL receptor gene (LDLR). In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential as ~10% of FH cases are attributed to CNVs in LDLR; accounting for them decreases false negative findings...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28874441/comprehensive-analyses-of-oxidized-phospholipids-using-a-measured-ms-ms-spectra-library
#8
Ryohei Aoyagi, Kazutaka Ikeda, Yosuke Isobe, Makoto Arita
Oxidized phospholipids (OxPLs) are widely held to be associated with various diseases such as arteriosclerosis, diabetes and cancer. To characterize the structure-specific behavior of OxPLs and their physiological relevance, we developed a comprehensive analytical method by establishing a measured MS/MS spectra library of OxPLs . Biogenic OxPLs were prepared by the addition of specific oxidized fatty acids to cultured cells, where they were incorporated into cellular phospholipids, and untargeted lipidomics by LC-quadrupole/time-of-flight (QTOF) MS was applied to collect MS/MS spectra for the OxPLs...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28874440/blocking-gp130-signaling-suppresses-autotaxin-expression-in-adipocytes-and-improves-insulin-sensitivity-in-diet-induced-obesity
#9
Shuhong Sun, Ran Wang, Jianwen Song, Ming Guan, Na Li, Xiaotian Zhang, Zhenwen Zhao, Junjie Zhang
Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Up-regulation of ATX expression in obese patients and mice is closely related with insulin resistance and impaired glucose tolerance. However, the mechanism of ATX expression in adipocytes remains largely unknown. In this study, we found that gp130-mediated JAK-STAT3 activation was required for abundant ATX expression in adipocytes...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28870972/ldl-cholesterol-level-in-fifth-grade-school-children-associates-with-stature
#10
Lee A Pyles, Christa Lilly, Charles Mullett, Emily Polak, Eloise Elliott, William A Neal
Short stature is associated with increased LDL- cholesterol levels and coronary artery disease in adults. We investigated the relationship of stature to LDL levels in children in the West Virginia Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project to determine if the genetically determined inverse relationship observed in adults will be evident in 5th graders. A cross-sectional survey of schoolchildren was assessed for cardiovascular risk factors. Data collected at school screenings over 18 years in WV schools were analyzed for 63,152 5th graders to determine relationship of LDL to stature with consideration of age, gender and BMI...
September 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28870971/polygenic-determinants-in-extremes-of-high-density-lipoprotein-cholesterol
#11
Jacqueline S Dron, Jian Wang, Cécile Low-Kam, Sumeet A Khetarpal, John F Robinson, Adam D McIntyre, Matthew R Ban, Henian Cao, David Rhainds, Marie-Pierre Dubé, Daniel J Rader, Guillaume Lettre, Jean-Claude Tardif, Robert A Hegele
HDL cholesterol (HDL-C) remains a superior biochemical predictor of cardiovascular disease risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery sample of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score...
September 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28830907/plasma-cholesterol-homeostasis-hdl-remodeling-and-function-during-the-acute-phase-reaction
#12
Francesca Zimetti, Stefano De Vuono, Monica Gomaraschi, Maria Pia Adorni, Elda Favari, Nicoletta Ronda, Maria Anastasia Ricci, Fabrizio Veglia, Laura Calabresi, Graziana Lupattelli
Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44...
August 22, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28822960/loss-of-perilipin-2-in-cultured-myotubes-enhances-lipolysis-and-redirects-the-metabolic-energy-balance-from-glucose-oxidation-towards-fatty-acid-oxidation
#13
Yuan Z Feng, Jenny Lund, Yuchuan Li, Irlin K Knabenes, Siril S Bakke, Eili Tranheim Kase, Yun K Lee, Alan R Kimmel, G Hege Thoresen, Arild Christian Rustan, Knut Tomas Dalen
Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2-/- mice contain reduced content of LDs and accumulate less oleic acid in triacylglycerol (TAG), due to elevated LD hydrolysis compared to Plin2+/+ myotubes. The reduced ability to store TAG in LDs in Plin2-/- myotubes is accompanied by a shift in energy metabolism...
August 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28818873/modulation-of-the-membrane-dipole-potential-a-prospective-mechanism-to-differentiate-anaesthetic-non-anaesthetic-activity-and-a-tool-to-assess-susceptibility
#14
Benjamin Michael Davis, Jonathan Brenton, Sterenn Davis, Ehtesham Shamsher, Claudia Sisa, Ljuban Grgic, M Francesca Cordeiro
There is great individual variation in response to general anaesthetics leading to difficulties in optimal dosing and sometimes even accidental awareness during general anaesthesia (AAGA). AAGA is a rare but potentially devastating complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel, personalised screening techniques to accurately predict a patient's response to GA and the risk of AAGA remains an unmet clinical need. In the present study we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anaesthetic activity using a well-described inducer/non-inducer pair...
August 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28814641/ceramide-activation-of-rhoa-rho-kinase-impairs-actin-polymerization-during-aggregated-ldl-catabolism
#15
Rajesh K Singh, Abigail S Haka, Alexandria Brumfield, Inna Grosheva, Priya Bhardwaj, Harvey F Chin, Yuquan Xiong, Timothy Hla, Frederick R Maxfield
Macrophages use an extracellular, hydrolytic compartment formed by local actin polymerization to digest aggregated LDL (agLDL). Catabolism of agLDL promotes foam cell formation and creates an environment rich in LDL catabolites including cholesterol and ceramide. Increased ceramide levels are present in lesional LDL, but the effect of ceramide on macrophage pro-atherogenic processes remains unknown. Here, we show that macrophages accumulate ceramide in atherosclerotic lesions. Using macrophages from Sphingosine Kinase 2 knockout (SK2KO) mice to mimic ceramide rich conditions of atherosclerotic lesions, we show that SK2KO macrophages display impaired actin polymerization and foam cell formation in response to contact with agLDL...
August 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28814640/agpat4-lpaat%C3%AE-deficiency-highlights-the-molecular-heterogeneity-of-epididymal-and-perirenal-white-adipose-depots
#16
Emily B Mardian, Ryan M Bradley, Juan J Aristizabal Henao, Phillip M Marvyn, Katherine A Moes, Eric Bombardier, A Russell Tupling, Ken D Stark, Robin E Duncan
Acylglycerophosphate acyltransferase 4 (AGPAT4)/lysophosphatidic acid acyltransferase delta (LPAATδ) catalyzes the formation of phosphatidic acid (PA), a precursor of triacylglycerol (TAG). We investigated the effect of Agpat4 gene ablation on white adipose tissue (WAT), after finding consistent expression across depots. Epididymal WAT mass was 40% larger in male Agpat4-/- mice than wildtype littermates, but unchanged in perirenal, retroperitoneal, and inguinal WAT and subscapular brown adipose tissue. Metabolic changes were identified in epididymal WAT that were not evident in perirenal WAT, which was analyzed for comparison...
August 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28814639/deposition-and-hydrolysis-of-serine-dipeptide-lipids-of-bacteroidetes-bacteria-in-human-arteries-relationship-to-atherosclerosis
#17
Reza Nemati, Christopher Dietz, Emily J Anstadt, Jorge Cervantes, Yaling Liu, Floyd E Dewhirst, Robert B Clark, Sydney Finegold, James J Gallagher, Michael B Smith, Xudong Yao, Frank C Nichols
Multiple reaction monitoring mass spectrometry (MRM-MS) analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes including Lipid 654, an agonist for human and mouse Toll-like receptor 2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes, and human serum and brain samples from healthy adults...
August 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28811322/analysis-of-sphingolipids-sterols-and-phospholipids-in-human-pathogenic-cryptococcus-strains
#18
Ashutosh Singh, Andrew MacKenzie, Geoffrey Girnun, Maurizio Del Poeta
Cryptococcus species cause invasive infections in humans. Lipids play an important role in the progression of these infections. Independent studies done by our group and others provide some detail about the functions of these lipids in Cryptococcus infections. However, pathways of biosynthesis and metabolism of these lipids are not completely understood. To thoroughly understand the physiological role of these Cryptococcus lipids, a proper structure and composition analyses of Cryptococcus lipids is demanded...
August 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28798072/the-roles-of-apo-a-size-phenotype-and-dominance-pattern-in-pcsk9-inhibition-induced-reduction-in-lp-a-with-alirocumab
#19
Byambaa Enkhmaa, Erdembileg Anuurad, Wei Zhang, Kun Yue, Ching-Shang Li, Lars Berglund
An elevated level of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a)-reduction with apolipoprotein(a) [apo(a)] size polymorphism, phenotype, and dominance pattern and LDL-C-reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from 2 clinical trials. Alirocumab significantly reduced total Lp(a) (pooled median: -21%, p=0...
August 10, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28768704/the-good-side-of-cholesterol-a-requirement-for-maintenance-of-intestinal-integrity
#20
David Y Hui
No abstract text is available yet for this article.
August 2, 2017: Journal of Lipid Research
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