抄録
Leptin is an adipocyte-secreted hormone that regulates body energy metabolism. We have recently shown that leptin stimulates fatty acid oxidation in skeletal muscle by activating α2 AMP-activated protein kinase (AMPK). Leptin exerts this effect directly at the level of muscle and through the hypothalamic-sympathetic nervous system. In contrast, hypothalamic α2 AMPK activity is inhibited by anorexigenic hormones (leptin and insulin), a melanocortin (MC) receptor agonist (anorexigen), high glucose and refeeding. AGRP (orexigenic neuropeptide), fasting and MC4 receptor-KO obese mouse increase hypothalamic AMPK activity. Expression of dominant-negative (DN) and constitutively active (CA) AMPK in the hypothalamus is sufficient to change food intake, body weight and expression of orexigenic neuropeptides such as NPY, AGRP and MCH. CA-AMPK blocks leptin-induced suppression of food intake. We recently examined the signaling pathway of leptin's effects on AMPK, using muscle and neuronal cell lines that express leptin receptor Ob-Rb. Leptin activates α2 but not α1 AMPK in muscle cells through activation of ataxia telangiectasia mutated and calcium/calmodulin-dependent protein kinase kinase β. Furthermore, cellular localization of α2 AMPK is changed in response to leptin. In contrast, leptin suppresses α2 AMPK activity and NPY expression in neuronal cells. Thus, leptin reciprocally regulates AMPK activity in neuronal and muscle cells. Our data indicate that leptin-AMPK system plays a critical role in peripheral and central regulation of body energy metabolism. [J Physiol Sci. 2006;56 Suppl:S27]
