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

Endocrinology. 2010 Nov;151(11):5157-64. doi: 10.1210/en.2010-0176. Epub 2010 Sep 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Caloric Restriction*
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Fibrosis
  • Glucose / metabolism
  • Insulin / metabolism*
  • Insulin Resistance*
  • Lipid Metabolism
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Obesity / metabolism
  • Oxidative Stress
  • Physical Conditioning, Animal*
  • Random Allocation
  • Rats

Substances

  • Insulin
  • Glucose