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Journal of Lipid Research

Rayane A Ghandour, Cecilia Colson, Maude Giroud, Stefanie Maurer, Samah Rekima, Gerard P Ailhaud, Martin Klingenspor, Ez-Zoubir Amri, Didier F Pisani
The recent characterization of functional brown adipose tissue (BAT) in adult humans has opened new perspectives for regulation of energy expenditure with respect to obesity and diabetes. Furthermore, dietary recommendations have taken into account the insufficient dietary intake of ω3 polyunsaturated fatty acids (PUFA) and the concomitant excessive intake of ω6 PUFA associated with the occurrence of overweight/obesity. We aimed to study whether ω3 PUFAs could play a role in the recruitment and function of energy-dissipating brown/brite adipocytes...
January 17, 2018: Journal of Lipid Research
Svenja Bockelmann, John G M Mina, Sergei Korneev, Dina G Hassan, Dagmar Mueller, Angelika Hilderink, Hedwich C Vlieg, Reinout Raijmakers, Albert J R Heck, Per Haberkant, Joost C M Holthuis
Ceramides are central intermediates of sphingolipid metabolism with dual roles as mediators of cellular stress signalling and mitochondrial apoptosis. How ceramides exert their cytotoxic effects is unclear and their poor solubility in water hampers a search for specific protein interaction partners. In here, we report the application of a photoactivatable and clickable ceramide analogue, pacCer, to identify ceramide binding proteins and unravel the structural basis by which these proteins recognize ceramide...
January 17, 2018: Journal of Lipid Research
Albert G Linden, Shili Li, Hwa Y Choi, Fei Fang, Masashi Fukasawa, Kosaku Uyeda, Robert E Hammer, Jay D Horton, Luke J Engelking, Guosheng Liang
Lipogenesis in liver is highest in the postprandial state; insulin activates SREBP-1c, which transcriptionally activates genes involved in fatty acid (FA) synthesis, whereas glucose activates ChREBP, which activates both glycolysis and FA synthesis. Whether SREBP-1c and ChREBP act independently of one another is unknown. Here, we characterized mice with liver-specific deletion of ChREBP (L-Chrebp-/- mice). Hepatic ChREBP deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes, particularly in response to sucrose refeeding following fasting, a dietary regimen that elicits maximal lipogenesis...
January 15, 2018: Journal of Lipid Research
Krishna M Padmanabha Das, Lisa Wechselberger, Márton Liziczai, Montserrat De la Rosa Rodriguez, Gernot F Grabner, Christoph Heier, Roland Viertlmayr, Claudia Radler, Joerg Lichtenegger, Robert Zimmermann, Jan Willem Borst, Rudolf Zechner, Sander Kersten, Monika Oberer
Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance of energy homeostasis. Hypoxia inducible lipid droplet associated protein (HILPDA)/Hypoxia inducible gene-2 (Hig-2) has been shown to affect intracellular TAG levels, yet, the underlying molecular mechanisms are unclear. Here, we show that HILPDA inhibits adipose triglyceride lipase (ATGL), the enzyme catalyzing the first step of intracellular TAG hydrolysis. HILPDA shares structural similarity with G0/G1 switch gene 2 (G0S2), an established inhibitor of ATGL...
January 11, 2018: Journal of Lipid Research
Michael J Pulkoski-Gross, Meredith L Jenkins, Jean-Philip Truman, Mohamed F Salama, Christopher J Clarke, John E Burke, Yusuf A Hannun, Lina M Obeid
Sphingosine kinase 1 (SK1) is a key enzyme which regulates a multitude of cellular processes including cellular growth, immune cell trafficking, and inflammation via the production of sphingosine-1-phosphate (S1P). To produce S1P, SK1 must access sphingosine directly from membranes. Despite the need for membrane access, the molecular mechanisms underlying SK1s direct membrane interaction remain unclear. Here, we identify a novel positively charged site on SK1 which is responsible for electrostatic interactions with membranes...
January 11, 2018: Journal of Lipid Research
Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D Spassieva, Erhard Bieberich
We reported that amyloid beta peptide (Abeta42) activated neutral sphingomyelinase 2 (nSMase2) thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in wild type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with Fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria...
January 10, 2018: Journal of Lipid Research
Jianguo Lin, Shizhong Zheng, Alan D Attie, Mark P Keller, David A Bernlohr, William S Blaner, Elizabeth P Newberry, Nicholas O Davidson, Anping Chen
Hepatic stellate cell (HSC) activation occurs along with decreased Perilipin5 (Plin5) and liver fatty acid-binding protein (L-Fabp) expression and coincident lipid droplet (LD) depletion. Conversely, the activated phenotype is reversible in wild type (wt) HSCs upon forced expression of Plin5. Here we asked if L-Fabp expression is required for Plin5-mediated rescue of the quiescent phenotype. Lentiviral Plin5 transduction of passaged L-Fabp-/- HSCs failed to reverse activation markers or to restore lipogenic gene expression and LD formation...
January 9, 2018: Journal of Lipid Research
Michael C Phillips
ATP-binding cassette transporter A1 (ABCA1) functions as a lipid transporter because it mediates the transfer of cellular phospholipid (PL) and free (unesterified) cholesterol (FC) to apolipoprotein (apo) A-I and related proteins present in the extracellular medium. ABCA1 is a membrane PL translocase and its enzymatic activity leads to transfer of PL molecules from the cytoplasmic leaflet to the exofacial leaflet of a cell plasma membrane. The presence of active ABCA1 in the plasma membrane promotes binding of apoA-I to the cell surface...
January 5, 2018: Journal of Lipid Research
Liudmila L Mazaleuskaya, Ashkan Salamatipour, Dimitra Sarantopoulou, Liwei Weng, Garret A FitzGerald, Ian A Blair, Clementina Mesaros
The biosynthesis of eicosanoids occurs enzymatically via lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P450, or through non-enzymatic free radical reactions. The enzymatic routes are highly enantiospecific. Chiral separation and high sensitivity detection methods are required to differentiate and quantify enantioselective HETEs (hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acids) in complex biological fluids. We report here a targeted chiral lipidomics analysis of human blood using ultrahigh performance liquid chromatgraphy (UHPLC)-electron capture atmospheric pressure chemical ionization/high resolution mass spectrometry (ECAPCI/HRMS)...
January 4, 2018: Journal of Lipid Research
Ying Liu, Zhuo Wei, Xingzhe Ma, Xiaoxiao Yang, Yuanli Chen, Lei Sun, Chuanrui Ma, Qing R Miao, David P Hajjar, Jihong Han, Yajun Duan
Cholesterol 25-hydroxylase (CH25H) catalyzes the production of 25-hydroxycholesterol (25-HC), an oxysterol which can play an important role in different biological processes. However, the mechanisms regulating CH25H expression have not been fully elucidated. In this study, we determined that CH25H is highly expressed in mouse liver and peritoneal macrophages. We identified several liver X receptor (LXR) response elements (LXREs) in the human CH25H promoter. In HepG2 cells, activation of LXR by 25-HC or other oxysterols and synthetic ligands [T0901317 (T317) and GW3965] induced CH25H protein expression which was associated with increased CH25H mRNA expression...
January 3, 2018: Journal of Lipid Research
Jessica M Lee, Jessica R Ong, Laurent Vergnes, Thomas Q de Aguiar Vallim, Jonathan Nolan, Rita M Cantor, Julian R F Walters, Karen Reue
Diet1 modulates intestinal production of the hormone fibroblast growth factor 15 (FGF15), which signals in liver to regulate bile acid synthesis. C57BL/6ByJ mice with a spontaneous Diet1 null mutation are resistant to hypercholesterolemia compared to wild-type C57BL/6J mice through enhanced cholesterol conversion to bile acids. To further characterize the role of Diet1 in metabolism, we generated Diet1-/- mice on the C57BL6/J genetic background. C57BL/6J Diet1-/- mice had elevated bile acid levels, reduced Fgf15 expression, and increased gastrointestinal motility and intestinal luminal water content, which are symptoms of bile acid diarrhea (BAD) in humans...
January 2, 2018: Journal of Lipid Research
William J Valentine, Suzumi M Tokuoka, Daisuke Hishikawa, Yoshihiro Kita, Hideo Shindou, Takao Shimizu
Adaption of skeletal muscle to endurance exercise includes PPARδ- and AMP-activated protein kinase (AMPK) / PPARγ coactivator 1α (PGC1α) -mediated transcriptional responses that result in increased oxidative capacity and conversion of glycolytic to more oxidative fiber types. These changes are associated with whole-body metabolic alterations including improved glucose handling and resistance to obesity. Increased docosahexaenoic acid (DHA; 22:6n-3) content in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is also reported in endurance exercise-trained glycolytic muscle; however, the DHA-metabolizing enzymes involved and biological significance of the enhanced DHA content are unknown...
December 28, 2017: Journal of Lipid Research
Sergei A Novgorodov, Joshua R Voltin, Monika A Gooz, Li Li, John J Lemasters, Tatyana I Gudz
Inhibiting the glutamate/cystine antiporter system xc-, a key antioxidant defense machinery in the CNS, could trigger a novel form of regulated necrotic cell death, ferroptosis. The underlying mechanisms of system xc--dependent cell demise were elucidated using primary oligodendrocytes (OLs) treated with glutamate to block system xc- function. Pharmacological analysis revealed ferroptosis as a major contributing factor to glutamate-initiated OL death. Sphingolipid profile showed elevations of ceramide species and sphingosine that were preventable by inhibiting of an acid sphingomyelinase (ASM) activity...
December 27, 2017: Journal of Lipid Research
Lisa R Tannock, Maria C De Beer, Ailing Ji, Preetha Shridas, Victoria P Noffsinger, Laura den Hartigh, Alan Chait, Frederick C de Beer, Nancy R Webb
Serum amyloid A (SAA) is a family of acute phase reactants. Plasma levels of human SAA1/SAA2 (mouse SAA1.1/2.1) can increase >1000-fold during an acute phase response. Mice, but not humans, express a third relatively understudied SAA isoform, SAA3. We investigated whether mouse SAA3 is an HDL-associated acute phase SAA. qRT-PCR with isoform-specific primers indicated that SAA3 and SAA1.1/2.1 are induced similarly in livers (~2500-fold vs ~6000-fold, respectively) and fat (~400-fold vs ~100-fold, respectively) of LPS-injected mice...
December 15, 2017: Journal of Lipid Research
Kelli M Sas, Jiahe Lin, Thekkelnaycke M Rajendiran, Tanu Soni, Viji Nair, Lucy M Hinder, Hosagrahar V Jagadish, Thomas W Gardner, Steven F Abcouwer, Frank C Brosius, Eva L Feldman, Matthias Kretzler, George Michailidis, Subramaniam Pennathur
Lipids are ubiquitous metabolites with diverse functions; abnormalities in lipid metabolism appear related to complications from multiple diseases, including type 2 diabetes. Through technological advances, the entire lipidome has been characterized, and researchers now need computational approaches to better understand lipid network perturbations in different diseases. Using a mouse model of type 2 diabetes with microvascular complications, we examined lipid levels in plasma and in renal, neural, and retinal tissues to identify shared and distinct lipid abnormalities...
December 13, 2017: Journal of Lipid Research
Emmani B M Nascimento, Louise Mannerås Holm, Alexander V Chibalin, Marie Björnholm, Juleen R Zierath
Conversion of diacylglycerol to phosphatidic acid is mediated by diacylglycerol kinases (DGK), with DGKα specifically linked to adaptive immune responses. We determined the role of DGKα in obesity and inflammatory responses to a high fat diet (HFD). DGKα knockout (KO) and wild-type (WT) littermates were either a) chow-fed, b) HFD-fed for 12 weeks (Long-Term HFD), or c) HFD-fed for 3 days (Acute HFD). Body weight/composition, oxygen consumption, food intake and glucose tolerance (IPGT) was unaltered between chow-fed DGKα KO and WT mice...
December 12, 2017: Journal of Lipid Research
John R Montford, Allison M B Lehman, Colin D Bauer, Jelena Klawitter, Jost Klawitter, Joanna M Poczobutt, Micah Scobey, Mary Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
The group IVA calcium dependent cytosolic phospholipase A2 enzyme (cPLA2α) directs a complex eicosanoid storm which accompanies the tissue response to injury. cPLA2α, and its downstream eicosanoid mediators, are also implicated in the pathogenesis of fibrosis in many organs including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). Wild type (WT) C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice (WT-BMT) or mice deficient in cPLA2α (KO-BMT)...
December 11, 2017: Journal of Lipid Research
Adam H Metherel, R J Scott Lacombe, Rapha Eumll Chouinard-Watkins, Kathryn E Hopperton, Richard P Bazinet
Previous assessments of the PUFA biosynthesis pathway have focused on DHA and arachidonic acid synthesis. Here, we determined whole-body synthesis-secretion kinetics for all downstream products of PUFA metabolism, including direct measurements of DHA and n-6 docosapentaenoic acid (DPAn-6, 22:5n-6) turnover, and compared n-6 and n-3 homologue kinetics. We infused labeled α-linolenic acid (ALA, 18:3n-3), linoleic acid (LNA, 18:2n-6), DHA and DPAn-6 as 2H5-ALA, 13C18-LNA, 13C22-DHA or 13C22-DPAn-6. Eight 11-week-old Long Evans rats fed a 10% fat diet were infused with the labeled PUFAs over 3 h, and plasma enrichment of labeled products was measured every 30 min...
December 11, 2017: Journal of Lipid Research
Xinchen Qiu, Jian Li, Sihan Lv, Jiamin Yu, Junkun Jiang, Jindong Yao, Yang Xiao, Bingxin Xu, Haiyan He, Fangfei Guo, Zhen-Ning Zhang, Chao Zhang, Bing Luan
Disregulation of fatty acid oxidation, one of the major mechanisms to maintain hepatic lipid homeostasis under fasting conditions, leads to hepatic steatosis. Although obesity and type 2 diabetes-induced ER stress contributes to hepatic steatosis, it is largely unknown how ER stress regulates fatty acid oxidation. Here we show that fasting glucagon stimulates the dephosphorylation and nuclear translocation of HDAC5, where it interacts with PPARα and promotes transcriptional activity of PPARα. As a result, overexpression of HDAC5 but not PPARα binding-deficient HDAC5 in liver improves lipid homeostasis, while RNAi-mediated knockdown of HDAC5 deteriorates hepatic steatosis...
December 11, 2017: Journal of Lipid Research
Walter A Boiten, Tineke Berkers, Samira Absalah, Jeroen van Smeden, Adriana P M Lavrijsen, Joke A Bouwstra
Restoring the lipid homeostasis of the stratum corneum (SC) is a common strategy to enhance the skin barrier function. Here, we used a ceramide containing vernix caseosa (VC) based formulation and were able to accelerate barrier recovery in healthy volunteers. The recovery was examined over 16 days by monitoring trans-epidermal water loss (TEWL) after barrier disruption by tape-stripping. Four skin sites were used to examine the effects of both treatment and barrier recovery. After 16 days, samples were harvested at these sites to examine the SC ceramide composition and the lipid organization...
December 7, 2017: Journal of Lipid Research
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