title: BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions.
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.
authors.affiliation: Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, UK. ajw232@cam.ac.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Whittle
authors.forename: Stefania
authors.initials: S
authors.lastname: Carobbio
authors.forename: Luís
authors.initials: L
authors.lastname: Martins
authors.forename: Marc
authors.initials: M
authors.lastname: Slawik
authors.forename: Elayne
authors.initials: E
authors.lastname: Hondares
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Vázquez
authors.forename: Donald
authors.initials: D
authors.lastname: Morgan
authors.forename: Robert I
authors.initials: RI
authors.lastname: Csikasz
authors.forename: Rosalía
authors.initials: R
authors.lastname: Gallego
authors.forename: Sergio
authors.initials: S
authors.lastname: Rodriguez-Cuenca
authors.forename: Martin
authors.initials: M
authors.lastname: Dale
authors.forename: Samuel
authors.initials: S
authors.lastname: Virtue
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004734:Energy Metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022722:Thermogenesis
chemical_list: C415983:Bmp8b protein, mouse; D019485:Bone Morphogenetic Proteins; D055372:AMP-Activated Protein Kinases; D009638:Norepinephrine