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 NH(2)-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.
Sabio
Guadalupe
G
Howard Hughes Medical Institute, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Kennedy
Norman J
NJ
Cavanagh-Kyros
Julie
J
Jung
Dae Young
DY
Ko
Hwi Jin
HJ
Ong
Helena
H
Barrett
Tamera
T
Kim
Jason K
JK
Davis
Roger J
RJ
D000818:Animals; D004041:Dietary Fats; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D009928:Organ Specificity; D015398:Signal Transduction
D004041:Dietary Fats; D048055:Mitogen-Activated Protein Kinase 8