BMP-7最初是作为一种骨诱导剂(bone inducer)被发现的,但它还有很强的肾再生和神经再生效应。
现在,研究人员报告它能通过促进棕色(而不是白色)脂肪细胞的分化来调控体内能量平衡。BMP-7能够打开棕色脂肪的调控因子,包括PRDM16(见/biology/integrated/373602.shtml)和成脂肪转录因子,并且刺激线粒体的生物生成。BMP-7在小鼠体内的异位表达能增加棕色(而不是白色)脂肪质,导致能量消耗增多和体重增加减慢。这些结果对于肥胖症的治疗显然有参考价值。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 454, 1000-1004 (21 August 2008) | doi:10.1038/nature07221
New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure
Yu-Hua Tseng1, Efi Kokkotou3, Tim J. Schulz1, Tian Lian Huang1, Jonathon N. Winnay1, Cullen M. Taniguchi1, Thien T. Tran1, Ryo Suzuki1, Daniel O. Espinoza1, Yuji Yamamoto1, Molly J. Ahrens4, Andrew T. Dudley4, Andrew W. Norris5, Rohit N. Kulkarni2 & C. Ronald Kahn1
Section on Obesity and Hormone Action, and,
Section on Cell and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, 02215, USA
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, 02215, USA
Department of Biochemistry, Northwestern University, Evanston, Illinois 60208, USA
Division of Pediatric Endocrinology, University of Iowa Children's Hospital, Iowa City, Iowa 52242, USA
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-1 (peroxisome proliferator-activated receptor- (PPAR) coactivator-1; ref. 5), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPAR 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