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Garcia-Martin, R.* ; Alexaki, V.I.* ; Qin, N.* ; Rubin de Celis, M.F.* ; Economopoulou, M.* ; Ziogas, A.* ; Gercken, B.* ; Kotlabova, K.* ; Phieler, J.* ; Ehrhart-Bornstein, M.* ; Bornstein, S.R. ; Eisenhofer, G.* ; Breier, G.* ; Blueher, M.* ; Hampe, J.* ; El-Armouche, A.* ; Chatzigeorgiou, A. ; Chung, K.-J.* ; Chavakis, T.

Adipocyte-specific hypoxia-inducible factor 2α deficiency exacerbates obesity-induced brown adipose tissue dysfunction and metabolic dysregulation.

Mol. Cell. Biol. 36, 376-393 (2016)
Verlagsversion DOI
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Angiogenesis is a central regulator for white (WAT) and brown adipose tissue (BAT) adaptation in the course of obesity. Here we show that deletion of hypoxia-inducible factor 2α (HIF2α) in adipocytes (by using Fabp4-Cre transgenic mice), but not in myeloid or endothelial cells, negatively impacted on WAT angiogenesis and promoted WAT inflammation, WAT dysfunction, hepatosteatosis and systemic insulin resistance in obesity. Importantly, adipocyte HIF2α regulated vascular endothelial growth factor (VEGF) expression and angiogenesis of the obese BAT as well as its thermogenic function. Consistently, obese adipocyte-specific HIF2α-deficient mice displayed BAT dysregulation, associated with reduced levels of uncoupling protein-1 (UCP1) and a dysfunctional thermogenic response to cold exposure. VEGF administration reversed WAT and BAT inflammation and BAT dysfunction in adipocyte HIF2α-deficient mice. Together, adipocyte HIF2α is protective against maladaptation to obesity and metabolic dysregulation by promoting angiogenesis in both WAT and BAT and by counteracting obesity-mediated BAT dysfunction.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0270-7306
e-ISSN 1098-5549
Quellenangaben Band: 36, Heft: 3, Seiten: 376-393 Artikelnummer: , Supplement: ,
Verlag American Society for Microbiology (ASM)
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)