Leptin directly stimulates thermogenesis in skeletal muscle.

Using a method involving repeated oxygen uptake (MO(2)) determinations in skeletal muscle ex vivo, the addition of leptin was found to increase MO(2) in soleus muscles from lean mice. These effects were found to be inhibited by phosphatidylinositol 3-kinase inhibitors, absent in muscles from obese Lepr(db) mice which have the dysfunctional long form of leptin receptor, and blunted in muscles from diet-induced obese mice in the fed state but not during fasting. These findings indicate that leptin has direct thermogenic effects in skeletal muscle, and that these effects require both the long form of leptin receptors and phosphatidylinositol 3-kinase signalling.