JNK and obesity

The molecular links between obesity, insulin resistance and type 2 diabetes mellitus have been poorly understood. In the November 21 Nature, Jiro Hirosumi and colleagues describe a role for the c-Jun amino-terminal kinases (JNKs) in obesity (Nature, 420:333-336, November 21, 2002). JNK activity was elevated in both genetic and dietary murine models of obesity. Analysis of knockout mice showed that the jnk1 gene (but not the jnk2 gene) was essential for diet-induced obesity. The jnk1 knockout mice displayed reduced adipocyte size, decreased adiposity and adipose redistribution. The JNK1-deficiency also protected from obesity-induced insulin resistance, even when crossed with leptin-deficient obese mice.