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Cell Metab. 2014 Jun 3;19(6):981-92. doi: 10.1016/j.cmet.2014.03.032. Epub 2014 May 22.

Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.

Author information

1
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
2
Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden.
3
Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06520, USA.
4
Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden; RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, Yokohama, Kanagawa, 230-0045, Japan.
5
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden; Science for Life Laboratory, Solna, SE-171 21, Sweden.
6
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SE-141 86, Sweden; RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, Yokohama, Kanagawa, 230-0045, Japan.
7
Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: mark.horowitz@yale.edu.
8
Department of Medicine (H7), Karolinska Institutet, Stockholm, SE-141 86, Sweden. Electronic address: peter.arner@ki.se.

Abstract

White adipose tissue (WAT) morphology characterized by hypertrophy (i.e., fewer but larger adipocytes) associates with increased adipose inflammation, lipolysis, insulin resistance, and risk of diabetes. However, the causal relationships and the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1 as an adipocyte-expressed transcription factor with decreased expression/activity in WAT hypertrophy. In human adipocytes, the regulatory targets of EBF1 were enriched for genes controlling lipolysis and adipocyte morphology/differentiation, and in both humans and murine models, reduced EBF1 levels associated with increased lipolysis and adipose hypertrophy. Although EBF1 did not affect adipose inflammation, TNFα reduced EBF1 gene expression. High-fat diet intervention in Ebf1(+/-) mice resulted in more pronounced WAT hypertrophy and attenuated insulin sensitivity compared with wild-type littermate controls. We conclude that EBF1 is an important regulator of adipose morphology and fat cell lipolysis and may constitute a link between WAT inflammation, altered lipid metabolism, adipose hypertrophy, and insulin resistance.

PMID:
24856929
PMCID:
PMC4109056
DOI:
10.1016/j.cmet.2014.03.032
[Indexed for MEDLINE]
Free PMC Article
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