title: Cholesterol mobilization from hepatic lipid droplets during endotoxemia is altered in obese ob/ob mice.
abstract: The innate immune response to pathogens during the acute phase response includes lipid metabolism adaptations. Hepatic triacylglycerol (TG) and cholesteryl ester (CE) storage in and mobilization from lipid droplets (LDs) respond to metabolic changes under the control of liver X receptor (LXR) transactivation and cytokine transduction. To evaluate whether alterations of these mechanisms have an impact in the adaptive response to endotoxemia, we analysed liver metabolism changes in lipopolysaccharide (LPS)-treated ob/ob mice, which show altered metabolic and innate responses and a higher sensitivity to sepsis. Lipid composition of serum lipoproteins and hepatic LDs was determined in wild type and ob/ob mice 24 h after LPS treatment. Liver metabolic profiling was done by measuring enzyme activities and mRNA levels. Increased CE hydrolase activity in LDs from endotoxemic mice was accompanied by a lower content of CE and low or no induction of LXR-mediated expression of genes involved in HDL secretion. The attenuated response in liver lipid mobilization accompanied by the strain-specific cholesterol enrichment of secreted VLDL might lead to accumulation of LDL cholesterol. According to our findings, obese leptin-deficient mice present an altered control of hepatic lipid metabolism responses to LPS, which might be, in part at least, a consequence of impaired LXR.
authors.affiliation: Lipids & Liver Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Lino
authors.initials: L
authors.lastname: Arisqueta
authors.affiliation: Lipids & Liver Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Hiart
authors.initials: H
authors.lastname: Navarro-Imaz
authors.affiliation: Lipids & Liver Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Rueda
authors.affiliation: Lipids & Liver Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain olatz.fresnedo@ehu.es.
authors.forename: Olatz
authors.initials: O
authors.lastname: Fresnedo
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002788:Cholesterol Esters / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006937:Hypercholesterolemia / Q000209:etiology*; D015228:Hypertriglyceridemia / Q000209:etiology; D007113:Immunity, Innate / Q000187:drug effects; D066292:Lipid Droplets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000071518:Liver X Receptors; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000150:complications*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002788:Cholesterol Esters; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D014280:Triglycerides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D002787:Sterol Esterase
keywords: lipid; lipopolysaccharide; lipoprotein; liver; mouse