p70S6激酶丝氨酸491上的AMPK磷酸化以介导瘦素对食物摄入的影响

Summary

The PI3K-AKT, mTOR-p70S6 kinase and AMPK pathways play distinct and critical roles in metabolic regulation. Each pathway is necessary for leptin's anorexigenic effects in the hypothalamus. Here we show that these pathways converge in an integrated phosphorylation cascade to mediate leptin action in the hypothalamus. We identify serine⁴⁹¹ on α2AMPK as the site of convergence and show that p70S6 kinase forms a complex with α2AMPK, resulting in phosphorylation on serine⁴⁹¹. Blocking α2AMPK-serine⁴⁹¹phosphorylation increases hypothalamic AMPK activity, food intake, and body weight. Serine⁴⁹¹phosphorylation is necessary for leptin's effects on hypothalamic α2AMPK activ