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Diet-induced obesity is associated with hyperleptinemia, hyperinsulinemia, hepatic steatosis, and glomerulopathy in C57Bl/6J mice

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Abstract

Obesity and obesity-related illnesses are global epidemics impacting the health of adults and children. The purpose of the present work is to evaluate a genetically intact obese mouse model that more accurately reflects the impact of aging on diet-induced obesity and type 2 diabetes in humans. Male C57Bl/6J mice consumed either a control diet or one in which 60% kcal were due to lard beginning at 5–6 weeks of age. Body weight and fat measurements were obtained and necropsy performed at 15, 20, 30, and 40 weeks of age. Serum chemistry, histopathology, gene expression of the liver, and renal and hepatic function were also evaluated. In concert with significant increases in percent body fat and weight, mice fed the high-fat versus control diet had significantly increased levels of serum cholesterol. At ages 20 and 30 weeks, serum glucose was significantly higher in obese versus controls, while serum insulin levels were ≥4-fold higher in obese mice at ages 30 and 40 weeks. The effect of age exacerbated the effects of consuming a high-fat diet. In addition to being hyperinsulinemic and leptin resistant, older obese mice exhibited elevated hepatic PAI-1 and downregulation of GLUT4, G6PC, IGFBP-1, and leptin receptor mRNA in the liver, steatosis with subsequent inflammation, glomerular mesangial proliferation, elevated serum ALT, AST, and BUN, and increased numbers of pancreatic islets.

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Acknowledgements

We extend our thanks to Drs. Retha Newbold and Susan Elmore for their commentary and careful review of this manuscript. We also sincerely appreciate Dr. Grace Kissling for her assistance with the statistical analyses. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

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Authors and Affiliations

  1. Laboratory of Pharmacology, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA

    Undi Hoffler, Re Bai, Akef Rahman & Burhan I. Ghanayem

  2. Cellular and Molecular Pathology Branch, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

    Ralph Wilson, David Malarkey & Greg Travlos

  3. Integrated Laboratory Systems, Research Triangle Park, NC, USA

    Kristen Hobbie

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  1. Undi Hoffler
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Correspondence to Burhan I. Ghanayem.

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Hoffler, U., Hobbie, K., Wilson, R. et al. Diet-induced obesity is associated with hyperleptinemia, hyperinsulinemia, hepatic steatosis, and glomerulopathy in C57Bl/6J mice. Endocr 36, 311–325 (2009). https://doi.org/10.1007/s12020-009-9224-9

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