Adipocyte-Specific Overexpression of FOXC2 Prevents Diet-Induced Increases in Intramuscular Fatty Acyl CoA and Insulin Resistance

Insulin resistance plays a major role in the development of type 2 diabetes and may be causally associated with increased intracellular fat content. Transgenic mice with adipocyte-specific overexpression of FOXC2 (fork-head transcription factor) have been generated and shown to be protected against diet-induced obesity and glucose intolerance. To understand the underlying mechanism, we examined the effects of chronic high-fat feeding on tissue-specific insulin action and glucose metabolism in the FOXC2 transgenic (Tg) mice. Whole-body fat mass were significantly reduced in the FOXC2 Tg mice fed normal diet or high-fat diet compared with the wild-type mice. Diet-induced insulin resistance in skeletal muscle of the wild-type mice was associated with defects in insulin signaling and significant in