Role of Muscle c-Jun NH2-Terminal Kinase 1 in Obesity-Induced Insulin Resistance

Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH2-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1(-/-) mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (M-KO) mice exhibit improved insulin sensitivity compared with control wild-type (M-WT) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose tissue of HFD-fed M-WT mice but is suppressed only in the liver and adipose tissue of M-KO mice. These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity.