BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions

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• 作者：Andrew&#160 ; J. Whittle¹ ; ¹¹ ; ^{ajw232@cam.ac.uk} ; Stefania Carobbio¹ ; ¹¹ ; Luí ; s Martins² ; ³ ; ¹¹ ; Marc Slawik¹ ; ⁴ ; ¹¹ ; Elayne Hondares³ ; ⁵ ; Marí ; a&#160 ; Jesú ; s Vá ; zquez² ; ³ ; Donald Morgan⁶ ; Robert&#160 ; I. Csikasz⁸ ; Rosalí ; a Gallego⁹ ; Sergio Rodriguez-Cuenca¹ ; Martin Dale¹ ; Samuel Virtue¹ ; Francesc Villarroya³ ; ⁵ ; Barbara Cannon⁸ ; ¹⁰ ; Kamal Rahmouni⁶ ; ⁷ ; Miguel Ló ; pez² ; ³ ; Antonio Vidal-Puig¹ ; ^{ajv22@medschl.cam.ac.uk}
• 刊名：Cell
• 出版年：2012
• 期刊代码：50_00928674
• 类别：med
• 出版时间：11 May, 2012
• 卷：149
• 期：4
• 页码：871-885
• 文件大小：2162 K

摘要

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Summary

Thermogenesis in brown adipose tissue (BAT) is fundamental to energy balance and is also relevant for humans. Bone morphogenetic proteins (BMPs) regulate adipogenesis, and, here, we describe聽a role for BMP8B in the direct regulation of thermogenesis. BMP8B is induced by nutritional and thermogenic factors in mature BAT, increasing the response to noradrenaline through enhanced p38MAPK/CREB signaling and increased lipase activity. Bmp8b^{鈭?鈭?/sup>} mice exhibit impaired thermogenesis and reduced metabolic rate, causing weight gain despite hypophagia. BMP8B is also expressed in the hypothalamus, and Bmp8b^{鈭?鈭?/sup>} mice display altered neuropeptide levels and reduced phosphorylation of AMP-activated protein kinase (AMPK), indicating an聽anorexigenic state. Central BMP8B treatment increased sympathetic activation of BAT, dependent on the status of AMPK in key hypothalamic nuclei. Our results indicate that BMP8B is a thermogenic protein that regulates energy balance in partnership with hypothalamic AMPK. BMP8B may offer聽a mechanism to specifically increase energy dissipation by BAT.