Author/Authors :
Andrew J. Whittle، نويسنده , , Stefania Carobbio، نويسنده , , Luis Martins، نويسنده , , Marc Slawik، نويسنده , , Elayne Hondares، نويسنده , , Mar?a Jes?s V?zquez، نويسنده , , Donald Morgan، نويسنده , , Robert I. Csikasz، نويسنده , , Rosal?a Gallego، نويسنده , , Sergio Rodriguez-Cuenca، نويسنده , , Martin Dale، نويسنده , , Samuel Virtue، نويسنده , , Francesc Villarroya، نويسنده , , Barbara Cannon and Jan Nedergaard، نويسنده , , Kamal Rahmouni، نويسنده , , Miguel L?pez، نويسنده , , Antonio Vidal-Puig، نويسنده ,
Abstract :
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 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−/− mice exhibit impaired thermogenesis and reduced metabolic rate, causing weight gain despite hypophagia. BMP8B is also expressed in the hypothalamus, and Bmp8b−/− mice display altered neuropeptide levels and reduced phosphorylation of AMP-activated protein kinase (AMPK), indicating an 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 a mechanism to specifically increase energy dissipation by BAT.
