New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure (Nature, 2008, 454:1000-1004)

報告日期: 2008/11/04
報告時間: 16:00/16:50
報告學生: 徐宗溢
講評老師: 洪建中

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


Tseng et al., 2008 Nature 454:1000-1004


Speaker: Chung-Yi Hsu (徐宗溢)

Commentator: Dr. Jan-Jong Hung (洪建中)

Date: November 4, 2008

Time: 16:00-16:50

Place: Room 602


Obesity is resulted from an excess of energy intake (diet) relative to energy expenditure and adipose tissue is central to the regulation of energy balance. Two types of adipose tissue exist in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT stores energy and is the largest energy reserve in mammals, whereas BAT, expressing uncoupling protein (UCP) 1, can dissipate energy through adaptive thermogenesis. Factors that specify the development fate of white and brown adipose tissue remain poorly understood. Recently, bone morphogenetic protein (BMP) 4 has been implicated in the commitment of mesenchymal stem cells to the adipocyte lineage and BMP-2 is demonstrated as a strong inducer of adipogenic differentiation of white preadipocytes. BMPs are multi-functional growth factors that belong to the transforming growth factor b superfamily. BMPs have been shown to regulate embryonic development, neural development, cartilage and bone formation. The role of BMPs in the differentiation and function of BAT or the balance between WAT and BAT is unknown. In this study, the authors demonstrated that BMP7 promotes differentiation of brown, but not white, preadipocytes, in the absence of the normally required hormonal induction cocktail. BMP7 activated a full program of brown adipogenesis by suppression of early adipogenic inhibitors, induction of factors determining brown fat fate, increased expression of adipogenic transcription factors and induction of mitochondrial biogenesis. In addition, BMP7 triggered commitment of mesenchymal progenitor cells to the brown adipocyte lineage in both in vitro and ex vivo settings. Bmp7 knockout mice displayed a marked decrease in interscapular BAT mass and UCP1 protein. Mice that received adenovirus expressing BMP7 showed significant increases in brown fat mass, whole-body energy expenditure and basal body temperature, leading to a significant reduction in weight gain. These data reveal a novel function of BMP7 in the regulation of energy homeostasis by promoting brown, but not white, fat differentiation and function. Thus, treatment of humans with BMP7 may activate brown fat differentiation, leading to an increase in energy expenditure, and thereby providing a new way to combat obesity.