Caloric restriction reverses hepatic insulin resistance and steatosis in rats with low aerobic capacity

Thomas A. Bowman, Sadeesh K. Ramakrishnan, Meenakshi Kaw, Sang Jun Lee, Payal R. Patel, Varun K. Golla, Raymond E. Bourey, Per Magnus Haram, Lauren G. Koch, Steven L. Britton, Ulrik Wisløff, Abraham D. Lee, Sonia M. Najjar

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2-3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.

Original languageEnglish
Pages (from-to)5157-5164
Number of pages8
Issue number11
StatePublished - Nov 2010


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