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- Title
Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle.
- Authors
Kim, Jason K; Gimeno, Ruth E; Higashimori, Takamasa; Kim, Hyo-Jeong; Choi, Hyejeong; Punreddy, Sandhya; Mozell, Robin L; Tan, Guo; Stricker-Krongrad, Alain; Hirsch, David J; Fillmore, Jonathan J; Liu, Zhen-Xiang; Dong, Jianying; Cline, Gary; Stahl, Andreas; Lodish, Harvey F; Shulman, Gerald I
- Abstract
Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the effect of acute lipid infusion or chronic high-fat feeding on insulin action in FATP1 KO mice. Whole-body adiposity, adipose tissue expression of adiponectin, intramuscular fatty acid metabolites, and insulin sensitivity were not altered in FATP1 KO mice fed a regular chow diet. In contrast, FATP1 deletion protected the KO mice from fat-induced insulin resistance and intramuscular accumulation of fatty acyl-CoA without alteration in whole-body adiposity. These findings demonstrate an important role of intramuscular fatty acid metabolites in causing insulin resistance and suggest that FATP1 may be a novel therapeutic target for the treatment of insulin resistance and type 2 diabetes.
- Publication
The Journal of clinical investigation, 2004, Vol 113, Issue 5, p756
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI18917