Journal article
BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions
Cell (Cambridge), Vol.149(4), pp.871-885
05/11/2012
DOI: 10.1016/j.cell.2012.02.066
PMCID: PMC3383997
PMID: 22579288
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.
[Display omitted]
► BMP8B is expressed in BAT and is regulated in response to thermogenic stimuli ► BMP8B increases the thermogenic response of BAT to adrenergic stimulation ► Loss of BMP8B substantially increases susceptibility to diet-induced obesity ► BMP8B acts in the CNS to increase SNS activation of thermogenesis
Cold exposure and a high-fat diet trigger BMP8 signaling in brown adipose tissue and in the brain to boost energy expenditure.
Details
- Title: Subtitle
- BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions
- Creators
- Andrew J Whittle - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UKStefania Carobbio - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UKLuís Martins - Department of Physiology, School of Medicine-CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, SpainMarc Slawik - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UKElayne Hondares - CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, SpainMaría Jesús Vázquez - Department of Physiology, School of Medicine-CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, SpainDonald Morgan - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USARobert I Csikasz - The Wenner-Gren Institute, Stockholm University, Stockholm SE-106 91, SwedenRosalía Gallego - Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, Santiago de Compostela 15782, SpainSergio Rodriguez-Cuenca - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UKMartin Dale - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UKSamuel Virtue - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UKFrancesc Villarroya - CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, SpainBarbara Cannon - The Wenner-Gren Institute, Stockholm University, Stockholm SE-106 91, SwedenKamal Rahmouni - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USAMiguel López - Department of Physiology, School of Medicine-CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, SpainAntonio Vidal-Puig - Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.149(4), pp.871-885
- DOI
- 10.1016/j.cell.2012.02.066
- PMID
- 22579288
- PMCID
- PMC3383997
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/11/2012
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040472602771
Metrics
168 Record Views