New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure

Yu Hua Tseng, Efi Kokkotou, Tim J. Schulz, Tian Lian Huang, Jonathon N. Winnay, Cullen M. Taniguchi, Thien T. Tran, Ryo Suzuki, Daniel O. Espinoza, Yuji Yamamoto, Molly J. Ahrens, Andrew T. Dudley, Andrew W. Norris, Rohit N. Kulkarni, C. Ronald Kahn

Research output: Contribution to journalArticle

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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 obesity. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood. 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.

Original languageEnglish (US)
Pages (from-to)1000-1004
Number of pages5
JournalNature
Volume454
Issue number7207
DOIs
StatePublished - Aug 21 2008

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Bone Morphogenetic Protein 7
Adipogenesis
Brown Adipose Tissue
Energy Metabolism
Brown Adipocytes
White Adipose Tissue
Peroxisome Proliferator-Activated Receptors
Adipose Tissue
Obesity
White Adipocytes
CCAAT-Enhancer-Binding Proteins
Bone Morphogenetic Proteins
Thermogenesis
Organelle Biogenesis
p38 Mitogen-Activated Protein Kinases
Mesenchymal Stromal Cells
Nude Mice
Weight Gain
Mammals
Triglycerides

ASJC Scopus subject areas

  • General

Cite this

Tseng, Y. H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., ... Kahn, C. R. (2008). New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature, 454(7207), 1000-1004. https://doi.org/10.1038/nature07221

New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. / Tseng, Yu Hua; Kokkotou, Efi; Schulz, Tim J.; Huang, Tian Lian; Winnay, Jonathon N.; Taniguchi, Cullen M.; Tran, Thien T.; Suzuki, Ryo; Espinoza, Daniel O.; Yamamoto, Yuji; Ahrens, Molly J.; Dudley, Andrew T.; Norris, Andrew W.; Kulkarni, Rohit N.; Kahn, C. Ronald.

In: Nature, Vol. 454, No. 7207, 21.08.2008, p. 1000-1004.

Research output: Contribution to journalArticle

Tseng, YH, Kokkotou, E, Schulz, TJ, Huang, TL, Winnay, JN, Taniguchi, CM, Tran, TT, Suzuki, R, Espinoza, DO, Yamamoto, Y, Ahrens, MJ, Dudley, AT, Norris, AW, Kulkarni, RN & Kahn, CR 2008, 'New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure', Nature, vol. 454, no. 7207, pp. 1000-1004. https://doi.org/10.1038/nature07221
Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008 Aug 21;454(7207):1000-1004. https://doi.org/10.1038/nature07221
Tseng, Yu Hua ; Kokkotou, Efi ; Schulz, Tim J. ; Huang, Tian Lian ; Winnay, Jonathon N. ; Taniguchi, Cullen M. ; Tran, Thien T. ; Suzuki, Ryo ; Espinoza, Daniel O. ; Yamamoto, Yuji ; Ahrens, Molly J. ; Dudley, Andrew T. ; Norris, Andrew W. ; Kulkarni, Rohit N. ; Kahn, C. Ronald. / New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. In: Nature. 2008 ; Vol. 454, No. 7207. pp. 1000-1004.
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