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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology*
  • Adipogenesis / genetics
  • Adipogenesis / physiology*
  • Adipose Tissue, White / cytology*
  • Adiposity
  • Animals
  • Cells, Cultured
  • Diabetes Mellitus / pathology
  • Diet, High-Fat
  • Female
  • Gene Expression
  • Humans
  • Hypertrophy
  • Inflammation / pathology
  • Insulin Resistance / physiology
  • Lipolysis / genetics
  • Lipolysis / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA Interference
  • RNA, Small Interfering
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism


  • EBF1 protein, human
  • RNA, Small Interfering
  • Trans-Activators
  • Tumor Necrosis Factor-alpha