A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance

作者：Martins Luis; Seoane Collazo Patricia; Contreras Cristina; Gonzalez Garcia Ismael; Martinez Sanchez Noelia; Gonzalez Francisco; Zalvide Juan; Gallego Rosalia; Dieguez Carlos; Nogueiras Ruben; Tena Sempere Manuel; Lopez Miguel

来源：Cell Reports, 2016, 16(8): 2231-2242.

DOI：10.1016/j.celrep.2016.07.045

AMP-activated protein kinase (AMPK) in the ventromedial nucleus of the hypothalamus (VMH) and orexin (OX) in the lateral hypothalamic area (LHA) modulate brown adipose tissue (BAT) thermogenesis. However, whether these two molecular mechanisms act jointly or independently is unclear. Here, we show that the thermogenic effect of bone morphogenetic protein 8B (BMP8B) is mediated by the inhibition of AMPK in the VMH and the subsequent increase in OX signaling via the OX receptor 1 (OX1R). Accordingly, the thermogenic effect of BMP8B is totally absent in ox-null mice. BMP8B also induces browning of white adipose tissue (WAT), its thermogenic effect is sexually dimorphic (only observed in females), and its impact on OX expression and thermogenesis is abolished by the knockdown of glutamate vesicular transporter 2 (VGLUT2), implicating glutamatergic signaling. Overall, our data uncover a central network controlling energy homeostasis that may be of considerable relevance for obesity and metabolic disorders.

• 出版日期2016-8-23