Leptin is a hormone secreted by adipocytes that controls the lipid stores in muscles via signaling mechanisms that remain unclear. In January 17 Nature, Yasuhiko Minokoshi and colleagues from Harvard Medical School, Boston, show that the 5'-AMP-activated protein kinase (AMPK) is the essential mediator of the effects of leptin on fatty-acid metabolism in muscle.

Minokoshi et al. used a murine model and observed that leptin selectively stimulates phosphorylation and activation of the α2 catalytic subunit of AMPK (a2 AMPK) in skeletal muscle. Early activation of AMPK occurs by leptin acting directly on muscle, whereas later activation depends on leptin functioning through the hypothalamic-sympathetic nervous system axis. In addition, leptin suppresses the activity of acetyl coenzyme A carboxylase (ACC), stimulating the oxidation of fatty acids (Nature 2002, 415:339-343).

"Therefore, the AMPK pathway might provide targets for therapeutic agents to reduce lipotoxicity in obesity and type 2...