title: Response to a long-term high-fat diet in the signature of genes involved in lipid metabolism in ApoE(-/-) mice.
abstract: High-fat diet (HFD)-induced lipid metabolism disorders are a critical feature of diet-induced insulin resistance (IR); however, the mechanisms underlying the tissue-specific effects of HFDs on the signature of genes involved in lipid metabolism have not been fully investigated. Glucose homeostasis and insulin sensitivity were monitored in chow-fed and HFD-fed ApoE mice using the hyperinsulinemic-euglycemic clamp technique. The signatures of genes involved in lipid metabolism were measured in the liver and adipose tissues by quantitative real-time polymerase chain reaction and Western blot analysis. Long-term HFD (for 16 weeks) resulted in marked abnormalities in glucose and lipid metabolism and induced IR in ApoE mice. Long-term HFD also markedly upregulated the messenger RNA (mRNA) expression of insulin-induced gene-2, sterol regulatory element-binding protein cleavage-activating protein and sterol regulatory element-binding protein-1 in the liver and/or adipose tissues, in parallel with an elevated insulin-induced gene-2 protein in the liver. However, HFD markedly downregulated the mRNA expression of sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and low-density lipoprotein receptor in the liver. Interestingly, long-term HFD markedly decreased adipose triglyceride lipase and peroxisome proliferator-activated receptor-γ mRNA, and adipose triglyceride lipase protein contents in the liver and/or adipose tissues. These findings provide a framework to understand the mechanisms by which long-term HFD regulates the gene signatures involved in lipid metabolism in the pathogenesis of diet-induced IR.
authors.affiliation: The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.forename: Shengbing
authors.initials: S
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D059305:Diet, High-Fat; D064429:Fatty Acid Synthases / Q000235:genetics; D005786:Gene Expression Regulation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008049:Lipase / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D002787:Sterol Esterase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics; D000217:Acyltransferases
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D064429:Fatty Acid Synthases; D006903:Hydroxymethylglutaryl CoA Reductases; D047908:Intracellular Signaling Peptides and Proteins; D008049:Lipase; D008565:Membrane Proteins; D047495:PPAR gamma; D011973:Receptors, LDL; D002787:Sterol Esterase; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; C506119:Insig1 protein, mouse; C506120:Insig2 protein, mouse; C102196:SREBP cleavage-activating protein; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases