Less JNK, Less Fat

Science's STKE  26 Nov 2002:
Vol. 2002, Issue 160, pp. tw438-TW438
DOI: 10.1126/stke.2002.160.tw438

There is a correlation between obesity and insulin resistance, but the molecular mechanisms responsible for this connection are not evident. The c-Jun amino-terminal kinases (JNKs) interfere with insulin action, and Hirosumi et al. now report that JNK1 activity is indeed increased in obesity. In both dietary and genetic mouse models of obesity, JNK1 activity was increased in liver, muscle, and adipose tissues. Mice lacking JNK1 exhibited decreased adipocyte size and overall adiposity relative to wild-type mice. The JNK1-null mice did not gain as much weight as wild-type counterparts on a high-fat diet and had much lower blood glucose concentrations. In the absence of JNK1, serine phosphorylation of insulin receptor substrate-1 (IRS-1) , which is an inhibitory modification, decreased. In contrast, tyrosine phosphorylation of IRS-1 increased, which suggests enhanced insulin receptor signaling in the JNK1-null mice. The study shows that JNK1-deficiency may offer some protection against obesity-related insulin resistance.

J. Hirosumi, G. Tuncman, L. Chang, C. Z. Görgün, K. T. Uysal, K. Maeda, M. Karin, G. S. Hotamisligil, A central role for JNK in obesity and insulin resistance. Nature 420, 333-336 (2002). [Online Journal]