Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling
Jeremie Boucher, Marcelo A Mori, Kevin Y Lee, Graham Smyth, Chong Wee Liew, Yazmin Macotela, Michael Rourk, Matthias Bluher, Steven J Russell, C Ronald Kahn
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2012
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..View full abstract
Awarded by NIH
Awarded by DERC
We thank K.C. Hayes and the staff of the Foster Biomedical Research Laboratory at Brandeis University for excellent care of the animals used in this study. We thank the Joslin Diabetes and Endocrinology Research Center Specialized assay (5P30 DK 36836) and Physiology cores, and the Longwood Small Animal Imaging Facility. We also thank Kate Ellacott and the staff of the Vanderbilt Mouse Metabolic Phenotyping Center for the energy expenditure studies. The Vanderbilt MMPC is supported by NIH Grant DK59637. This work was supported by NIH grants (DK31036 and DK82659), DERC grants (DK34834) and an American Diabetes Association mentor-based award.