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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.

Original publication

DOI

10.1016/j.celrep.2016.07.045

Type

Journal article

Journal

Cell Rep

Publication Date

23/08/2016

Volume

16

Pages

2231 - 2242

Keywords

AMP-Activated Protein Kinases, Adipose Tissue, Brown, Adipose Tissue, White, Animals, Body Weight, Bone Morphogenetic Proteins, Energy Metabolism, Female, Gene Expression Regulation, Glutamic Acid, Hypothalamic Area, Lateral, Male, Mice, Knockout, Orexin Receptors, Orexins, Rats, Rats, Sprague-Dawley, Sex Factors, Signal Transduction, Thermogenesis, Ventromedial Hypothalamic Nucleus, Vesicular Glutamate Transport Protein 2