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Involvement of lipid droplets in hepatic responses to lipopolysaccharide treatment in mice
Authors:Lino Arisqueta,Maitane Nuñ  ez-Garcia,Jesus Ogando,Itsaso Garcia-Arcos,Begoñ  a Ochoa,Patricia Aspichueta,Olatz Fresnedo,Yuri Rueda
Affiliation:Lipids & Liver Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Bº Sarriena s/n, 48940 Leioa, Spain
Abstract:Infection and inflammation induce important changes in lipid metabolism, which result in increased free fatty acids and triacylglycerol in plasma and altered high density lipoprotein (HDL) metabolism. Our aim was to elucidate whether hepatic lipid droplets (LDs) are involved in the adaptations of lipid metabolism to endotoxemia. We characterized the lipid content and several enzymatic activities in subcellular fractions and subpopulations of LDs from livers of mice 24 h after lipopolysaccharide (LPS) treatment and analyzed the expression of key genes involved in lipid management. Endotoxemic mice showed lower lipid content in LDs with decreased molar fraction of cholesteryl ester and higher diacylglycerol/triacylglycerol ratio as compared to their controls. They also showed a decrease in cytosolic triacylglycerol hydrolase activity, specifically in dense LDs, and in microsomal and cytosolic diacylglycerol hydrolase activity; concomitantly neutral lipid biosynthetic capacity and triacylglycerol levels in plasma lipoproteins increased. Together with the overexpression of genes involved in lipogenesis and HDL formation our results suggest that altered hepatic management of LD lipids in LPS-treated mice might be related to the channeled mobilization of triacylglycerol for very low density lipoprotein assembly and to the induction of cholesterol export.
Keywords:Abc, ATP-binding cassette   ACAT, acyl-coenzymeA:cholesterol acyltransferase   CE, cholesteryl ester   CEH, cholesteryl ester hydrolase   CK, cytokines   DG, diacylglycerol   DGAT, diacylglycerol acyltransferase   DGH, diacylglycerol hydrolase   FA, fatty acid   FC, unesterified free cholesterol   HPBCD, 2-hydroxypropyl-β-cyclodextrin   I/LDL, intermediate and low density lipoproteins   LD, lipid droplet   LPS, lipopolysaccharide   LXR, liver X receptor   MTP, microsomal transfer protein   PC, phosphatidylcholine   PE, phosphatidylethanolamine   PL, phospholipid   PNSN, postnuclear supernatant   PS, phosphatidylserine   SM, sphingomyelin   SREBP, sterol regulatory element-binding protein   T090, T0901317   TG, triacylglycerol   TGH, triacylglycerol hydrolase   TLC, thin layer chromatography   UE, unspecific esterase
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