Impaired Thermogenesis and Adipose Tissue Development in Mice with Fat-Specific Disruption of Insulin and IGF-1 Signalling

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Impaired Thermogenesis and Adipose Tissue Development in Mice with Fat-Specific Disruption of Insulin and IGF-1 Signalling

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Title: Impaired Thermogenesis and Adipose Tissue Development in Mice with Fat-Specific Disruption of Insulin and IGF-1 Signalling
Author: Boucher, Jeremie; Mori, Marcelo A.; Lee, Kevin Y.; Smyth, Graham; Liew, Chong-Wee; Macotela, Yazmin; Rourk, Michael; Bluher, Matthias; Russell, Steven J.; Kahn, C. Ronald

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Citation: Boucher, Jeremie, Marcelo A. Mori, Kevin Y. Lee, Graham Smyth, Chong Wee Liew, Yazmin Macotela, Michael Rourk, Matthias Bluher, Steven J. Russell, and C. Ronald Kahn. 2012. Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nature Communications 3(6): 902.
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Abstract: Insulin and insulin-like growth factor 1 (IGF-1) play 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 signaling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet (HFD) induced obesity and age- and HFD-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 \(4^{\circ}C\). Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to \(\beta3\)-receptor stimulation. Thus, insulin/IGF-1 signaling 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.
Published Version: doi:10.1038/ncomms1905
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529640/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10578988
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