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Endocrinology. 2017 Dec 1;158(12):4233-4245. doi: 10.1210/en.2017-00212.

Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A.

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Integrative Physiology and Metabolism Section, Joslin Diabetes Center, Harvard Medical School.
School of Biology and Ecology and Graduate School of Biomedical Sciences and Engineering, University of Maine.
Department of Neurological Surgery, Oregon Health & Science University.
School of Dentistry, University of Michigan.
Brigham and Women's Hospital and Harvard Medical School.
Harvard Stem Cell Institute, Harvard University.


The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein (BMP) 7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibited a lack of obesity, even on a 45% high-fat diet. This is because the brown adipose tissue (BAT) of KO animals exhibited increased sympathetic activation and greater thermogenic capacity owing to a reestablishment of energy balance, most likely stemming from a compensatory increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals given central BMP7 displayed increased energy expenditure and a specific increase in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy expenditure or BAT SNA. Together, we demonstrated an important role for hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A-mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD regulation of the sympathetic drive to BAT for thermogenesis.

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