2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue
Albert, Verena (Biozentrum, University of Basel)
Svensson, Kristoffer (Biozentrum, University of Basel)
Shimobayashi, Mitsugu (Biozentrum, University of Basel)
Colombi, Marco (Biozentrum, University of Basel)
Muñoz, Sergio (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Jimenez, Veronica (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Handschin, Christoph (Biozentrum, University of Basel)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Hall, Michael N. (Biozentrum, University of Basel)
Universitat Autònoma de Barcelona. Centre de Biotecnologia Animal i de Teràpia Gènica

Date:	2016
Abstract:	Activation of non-shivering thermogenesis () in brown adipose tissue () has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of and cold-induced glucose uptake. Mammalian target of rapamycin complex 2 (2) mediates insulin-stimulated glucose uptake in metabolic tissues, but its role in is unknown. We show that 2 is activated in brown adipocytes upon β-adrenergic stimulation. Furthermore, mice lacking 2 specifically in adipose tissue (AdRi mice) are hypothermic, display increased sensitivity to cold, and show impaired cold-induced glucose uptake and glycolysis. Restoration of glucose uptake in by overexpression of hexokinase or activated Akt2 was sufficient to increase body temperature and improve cold tolerance in AdRi mice. Thus, 2 in mediates temperature homeostasis via regulation of cold-induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation.
Grants:	Ministerio de Economía y Competitividad SAF 2014-54866-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR1669
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Brown adipose tissue ; Glucose uptake ; 2 ; Thermogenesis ; Metabolism
Published in:	EMBO Molecular Medicine, Vol. 8 (january 2016) , p. 232-246, ISSN 1757-4684

DOI: 10.15252/emmm.201505610
PMID: 26772600

15 p, 3.7 MB

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