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

Cell Reports
Anthony R AngueiraPatrick Seale

Abstract

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 ERRα and PGC1α. Together, these studies demonstrate that EBF proteins specify the developmental fate and control the adaptive cold response of brown adipocytes.

Citations

May 27, 2020·Molecular Medicine·Anna E PravednikovaYulii V Shidlovskii
Apr 18, 2020·The FEBS Journal·Mohammed Faiz HussainLawrence Kazak
Nov 25, 2020·Metabolites·Fernando Lizcano, Felipe Arroyave
Mar 19, 2021·Immunometabolism·Michael J Griffin
Apr 14, 2021·Nature Metabolism·Anthony R AngueiraPatrick Seale
Jul 10, 2021·Frontiers in Pharmacology·Xinzhi LiYi Zhun Zhu

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Datasets Mentioned

BETA
GSE144188

Methods Mentioned

BETA
nuclear magnetic resonance
Protein assay
PCR
Immunoprecipitation
RNaseq

Key Resources (RRID) Mentioned

IMSR_JAX

Software Mentioned

EnrichR
featureCounts
R
Homer
STAR aligner
edgeR
Cal

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