title: High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.
abstract: High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Dexi
authors.initials: D
authors.lastname: Liu
mesh_terms: D017667:Adipocytes / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000473:pathology*; D052436:Adipose Tissue, White / Q000473:pathology*; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000097:blood / Q000473:pathology*; D018149:Glucose Intolerance / Q000503:physiopathology; D006946:Hyperinsulinism / Q000097:blood / Q000473:pathology*; D007249:Inflammation / Q000097:blood / Q000473:pathology*; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D009765:Obesity / Q000097:blood / Q000473:pathology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain / Q000502:physiology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha