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Publication : Early B Cell Factor Activity Controls Developmental and Adaptive Thermogenic Gene Programming in Adipocytes.

First Author  Angueira AR Year  2020
Journal  Cell Rep Volume  30
Issue  9 Pages  2869-2878.e4
PubMed ID  32130892 Mgi Jnum  J:287644
Mgi Id  MGI:6416589 Doi  10.1016/j.celrep.2020.02.023
Citation  Angueira AR, et al. (2020) Early B Cell Factor Activity Controls Developmental and Adaptive Thermogenic Gene Programming in Adipocytes. Cell Rep 30(9):2869-2878.e4
abstractText  Brown adipose tissue (BAT) activity protects animals against hypothermia and represents a potential therapeutic target to combat obesity. The transcription factor early B cell factor-2 (EBF2) promotes brown adipocyte differentiation, but its roles in maintaining brown adipocyte fate and in stimulating BAT recruitment during cold exposure were unknown. We find that the deletion of Ebf2 in adipocytes of mice ablates BAT character and function, resulting in cold intolerance. Unexpectedly, prolonged exposure to cold restores the thermogenic profile and function of Ebf2 mutant BAT. Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. Adipocyte-specific deletion of both Ebf1 and Ebf2 abolishes BAT recruitment during chronic cold exposure. Mechanistically, EBF1 and EBF2 promote thermogenic gene transcription through increasing the expression and activity of ERRalpha and PGC1alpha. Together, these studies demonstrate that EBF proteins specify the developmental fate and control the adaptive cold response of brown adipocytes.
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