Journal article
New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure
Nature (London), Vol.454(7207), pp.1000-1004
08/21/2008
DOI: 10.1038/nature07221
PMCID: PMC2745972
PMID: 18719589
Abstract
Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity1. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood2,3. Here we demonstrate that whereas some members of the family of bone morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 (PR-domain-containing 16; ref. 4) and PGC-1α (peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α; ref. 5), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPARγ and CCAAT/enhancer-binding proteins (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways. Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. Adenoviral-mediated expression of BMP7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and a reduction in weight gain. These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity.
Details
- Title: Subtitle
- New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure
- Creators
- Yu-Hua Tseng - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MAEfi Kokkotou - Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MATim J Schulz - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MATian Lian Huang - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MAJonathon N Winnay - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MACullen M Taniguchi - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MAThien T Tran - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MARyo Suzuki - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MADaniel O Espinoza - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MAYuji Yamamoto - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MAMolly J Ahrens - Department of Biochemistry, Northwestern University, Evanston, ILAndrew T Dudley - Northwestern UniversityAndrew W Norris - Division of Pediatric Endocrinology, University of Iowa Children’s Hospital, Iowa City, IARohit N Kulkarni - Section on Cell and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MAC. Ronald Kahn - Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, MA
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.454(7207), pp.1000-1004
- DOI
- 10.1038/nature07221
- PMID
- 18719589
- PMCID
- PMC2745972
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 08/21/2008
- Academic Unit
- Endocrinology and Diabetes; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology
- Record Identifier
- 9984024543402771
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