Involvement of lipid droplets in hepatic responses to lipopolysaccharide treatment in mice |
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Authors: | Lino Arisqueta,Maitane Nuñ ez-Garcia,Jesus Ogando,Itsaso Garcia-Arcos,Begoñ a Ochoa,Patricia Aspichueta,Olatz Fresnedo,Yuri Rueda |
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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 |
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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. |
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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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