期刊
MOLECULAR METABOLISM
卷 5, 期 1, 页码 57-65出版社
ELSEVIER
DOI: 10.1016/j.molmet.2015.11.001
关键词
EBF2; Beige fat; Brown fat; Obesity; Thermogenesis
资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK103008, F32DK105743] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008216] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP2OD007288] Funding Source: NIH RePORTER
- NIDDK NIH HHS [R01 DK103008, R01 DK123356, F32 DK105743] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008216] Funding Source: Medline
- NIH HHS [DP2 OD007288] Funding Source: Medline
Objective: The induction of beige/brite adipose cells in white adipose tissue (WAT) is associated with protection against high fat diet-induced obesity and insulin resistance in animals. The helix-loop-helix transcription factor Early B-Cell Factor-2 (EBF2) regulates brown adipose tissue development. Here, we asked if EBF2 regulates beige fat cell biogenesis and protects animals against obesity. Methods: In addition to primary cell culture studies, we used Ebf2 knockout mice and mice overexpressing EBF2 in the adipose tissue to study the necessity and sufficiency of EBF2 to induce beiging in vivo. Results: We found that EBF2 is required for beige adipocyte development in mice. Subcutaneous WAT or primary adipose cell cultures from Ebf2 knockout mice did not induce Uncoupling Protein 1 (UCP1) or a thermogenic program following adrenergic stimulation. Conversely, overexpression of EBF2 in adipocyte cultures induced UCP1 expression and a brown-like/beige fat-selective differentiation program. Transgenic expression of Ebf2 in adipose tissues robustly stimulated beige adipocyte development in the WAT of mice, even while housed at thermoneutrality. EBF2 overexpression was sufficient to increase mitochondrial function in WAT and protect animals against high fat diet-induced weight gain. Conclusions: Taken together, our results demonstrate that EBF2 controls the beiging process and suggest that activation of EBF2 in WAT could be used to reduce obesity. (C) 2015 The Authors. Published by Elsevier GmbH.
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