Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway

Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
The FASEB Journal (Impact Factor: 5.04). 02/2012; 26(5):2187-96. DOI: 10.1096/fj.11-199067
Source: PubMed


Body weight is regulated by coordinating energy intake and energy expenditure. Transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling has been shown to regulate energy balance in lower organisms, but whether a similar pathway exists in mammals is unknown. We have previously demonstrated that BMP7 can regulate brown adipogenesis and energy expenditure. In the current study, we have uncovered a novel role for BMP7 in appetite regulation. Systemic treatment of diet-induced obese mice with BMP7 resulted in increased energy expenditure and decreased food intake, leading to a significant reduction in body weight and improvement of metabolic syndrome. Similar degrees of weight loss with reduced appetite were also observed in BMP7-treated ob/ob mice, suggesting a leptin-independent mechanism utilized by BMP7. Intracerebroventricular administration of BMP7 to mice led to an acute decrease in food intake, which was mediated, at least in part, by a central rapamycin-sensitive mTOR-p70S6 kinase pathway. Together, these results underscore the importance of BMP7 in regulating both food intake and energy expenditure, and suggest new therapeutic approaches for obesity and its comorbidities.

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Available from: Ryo Suzuki, Dec 29, 2015
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    • "COMMON GENES SHARED BY OBESITY, CRC AND OSTEOPOROSIS, AND PLAUSIBLE EVIDENCE SUPPORTING THEIR RELATIONSHIPS WITH THE THREE DISEASES. GENES OBESITY CRC OSTEOPOROSIS PPP1R15A* In the bone morphogenetic protein (BMP) signaling pathway, which regulates appetite [34] Mutations in the BMP pathway are related with colorectal carcinogenesis [35] In the bone morphogenetic protein signaling pathway, which are associated with bone-related diseases, such as osteoporosis [36] FOS diet-induced obesity is accompanied by alteration of FOS expression [37] Proto-oncogene, in the KEGG pathway of colorectal cancer [38] Mice lacking c-fos develop severe osteopetrosis [39] FOSB positive association between maternal obesity [40] Oncogene, regulators of cell proliferation, has a debatable impact on CRC patient survival [41] Overexpression of FosB increases bone formation [42] HADHA* Associated with multiple fatty acid metabolism pathways [43] Unknown. Associated with breast cancer [44] Unknown. "
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    • "Amino acids, glucose, and growth factors induce mTORC1 activation in the hypothalamus and reduce food intake. In addition to leucine and leptin, CNTF (Cota et al., 2008) and bone morphogenic protein 9 (BMP9; Townsend et al., 2012) also suppress food intake. Culture studies have revealed that these molecules elicit mTORC1 signaling in neuronal cells. "
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    • "Various circulating peptides have been shown to be capable of activating BAT via the hypothalamus, such as GLP-1 [28] and BMP8B, another member of the BMP family [29]. In addition, Townsend et al. [25] showed that central administration of BMP7 resulted in reduced food intake, confirming that BMP7 is at least capable of exerting central effects. However, it remains to be determined whether subcutaneously administered BMP7 is able to enter the hypothalamus to subsequently exert central actions. "
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