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

FASEB J. 2012 May;26(5):2187-96. doi: 10.1096/fj.11-199067. Epub 2012 Feb 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Appetite*
  • Bone Morphogenetic Protein 7 / administration & dosage
  • Bone Morphogenetic Protein 7 / physiology*
  • Cells, Cultured
  • In Situ Hybridization
  • Injections, Intraventricular
  • Mice
  • Obesity / physiopathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Bone Morphogenetic Protein 7
  • bmp7 protein, mouse
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse