title: Expression profile of hepatic genes related to lipid homeostasis in LSR heterozygous mice contributes to their increased response to high-fat diet.
abstract: Perturbations of lipid homeostasis manifest as dyslipidemias and obesity, which are significant risk factors for atherosclerosis and diabetes. Lipoprotein receptors in the liver are key players in the regulation of lipid homeostasis, among which the hepatic lipolysis stimulated lipoprotein receptor, LSR, was recently shown to play an important role in the removal of lipoproteins from the circulation during the postprandial phase. Since heterozygous LSR+/- mice demonstrate moderate dyslipidemia and develop higher body weight gain in response to high-fat diet compared with littermate LSR+/+ controls, we questioned if LSR heterozygosity could affect genes related to hepatic lipid metabolism. A target-specific qPCR array for 84 genes related to lipid metabolism was performed on mRNA isolated from livers of 6 mo old female LSR+/- mice and LSR+/+ littermates following a 6 wk period on a standard (STD) or high-fat diet (60% kcal, HFD). Of the 84 genes studied, 32 were significantly downregulated in STD-LSR+/- mice compared with STD-LSR+/+, a majority of which were PPARα target genes involved in lipid metabolism and transport, and insulin and adipokine-signaling pathways. Of these 32 genes, 80% were also modified in HFD-LSR+/+, suggesting that STD-LSR+/- mice demonstrated a predisposition towards a "high-fat"-like profile, which could reflect dysregulation of liver lipid homeostasis. Since similar profiles of genes were affected by either LSR heterozygosity or by high-fat diet, this would suggest that LSR is a key receptor in regulating hepatic lipid homeostasis, and whose downregulation combined with a Western-type diet may increase predisposition to diet-induced obesity.
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Samina
authors: S
authors: Akbar
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Anthony
authors: A
authors: Pinçon
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Marie-Claire
authors: MC
authors: Lanhers
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Thomas
authors: T
authors: Claudepierre
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Catherine
authors: C
authors: Corbier
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Lynn
authors: L
authors: Gregory-Pauron
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Catherine
authors: C
authors: Malaplate-Armand
authors: UMR 7365 CNRS IMOPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Athanase
authors: A
authors: Visvikis
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors: Thierry
authors: T
authors: Oster
authors: EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, Vandœuvre-lès-Nancy, France; frances.yen-potin@univ-lorraine.fr.|INSERM, Nancy, France; and.
authors: Frances T
authors: FT
authors: Yen
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006706:Homeostasis / Q000235:genetics*; D007328:Insulin / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000235:genetics; D018110:Receptors, Lipoprotein / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D015430:Weight Gain / Q000235:genetics
chemical_list: D007328:Insulin; D008055:Lipids; D018110:Receptors, Lipoprotein
keywords: dyslipidemia; hepatic lipid metabolism; high-fat diet; lipolysis stimulated lipoprotein receptor; obesity