Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

AUTOR(ES)

Kim, Jason K.

FONTE

American Society for Clinical Investigation

RESUMO

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.

Documentos Relacionados

• Prevention of fat-induced insulin resistance by salicylate
• Role of the glucosamine pathway in fat-induced insulin resistance.
• PKC-θ knockout mice are protected from fat-induced insulin resistance
• Is “fat-induced” muscle insulin resistance rapidly reversible?
• Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease