title: Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway.
abstract: 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.
authors.affiliation: Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Townsend
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Tian Lian
authors.initials: TL
authors.lastname: Huang
authors.forename: Enxuan
authors.initials: E
authors.lastname: Jing
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schulz
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.forename: Cullen M
authors.initials: CM
authors.lastname: Taniguchi
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Espinoza
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: McDougall
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Efi
authors.initials: E
authors.lastname: Kokkotou
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tseng
mesh_terms: D000818:Animals; D001066:Appetite; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage / Q000502:physiology*; D002478:Cells, Cultured; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D051379:Mice; D009765:Obesity / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D055419:Bone Morphogenetic Protein 7; C525820:bmp7 protein, mouse; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases