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

Luís Martins | Zendy; Patricia SeoaneCollazo | Zendy; Cristina Contreras | Zendy; Ismael GonzálezGarcía | Zendy; Noelia MartínezSánchez | Zendy; Francisco González | Zendy; Juan Zalvide | Zendy; Rosalı́a Gallego | Zendy; Carlos Diéguez | Zendy; Rubén Nogueiras | Zendy; Manuel TenaSempere | Zendy; Miguel López | Zendy

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

Author(s) -

Luís Martins,

Patricia SeoaneCollazo,

Cristina Contreras,

Ismael GonzálezGarcía,

Noelia MartínezSánchez,

Francisco González,

Juan Zalvide,

Rosalı́a Gallego,

Carlos Diéguez,

Rubén Nogueiras,

Manuel TenaSempere,

Miguel López

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.07.045

Subject(s) - ampk , thermogenesis , endocrinology , medicine , energy homeostasis , brown adipose tissue , white adipose tissue , glutamatergic , orexin , amp activated protein kinase , biology , signal transduction , protein kinase a , hypothalamus , microbiology and biotechnology , adipose tissue , chemistry , glutamate receptor , kinase , receptor , neuropeptide , obesity

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.

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