Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling

Nat Commun. 2012 Jun 12:3:902. doi: 10.1038/ncomms1905.

Abstract

Insulin and insulin-like growth factor 1 (IGF-1) have important roles in adipocyte differentiation, glucose tolerance and insulin sensitivity. Here to assess how these pathways can compensate for each other, we created mice with a double tissue-specific knockout of insulin and IGF-1 receptors to eliminate all insulin/IGF-1 signalling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet-induced obesity and age- and high fat diet-induced glucose intolerance. Energy expenditure was increased in FIGIRKO mice despite a >85% reduction in brown fat mass. However, FIGIRKO mice were unable to maintain body temperature when placed at 4 °C. Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to β3-receptor stimulation. Thus, insulin/IGF-1 signalling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate.

Publication types

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

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Animals
  • Body Composition / genetics
  • Body Composition / physiology
  • Cells, Cultured
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Temperature
  • Thermogenesis / genetics
  • Thermogenesis / physiology*

Substances

  • Insulin
  • Insulin-Like Growth Factor I