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

Boucher J, Mori MA, Lee KY, Smyth G, Liew CW, Macotela Y, Rourk M, Bluher M, Russell SJ, Kahn CR
Nat Commun. 2012 3: 902

PMID: 22692545 · PMCID: PMC3529640 · DOI:10.1038/ncomms1905

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.

MeSH Terms (13)

Adipocytes Adipose Tissue Animals Body Composition Cells, Cultured Energy Metabolism Insulin Insulin-Like Growth Factor I Male Mice Mice, Knockout Temperature Thermogenesis

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