Dnmt3b deficiency in Myf5+-brown fat precursor cells promotes obesity in female mice

Shirong Wang, Qiang Cao, Xin Cui, Jia Jing, Fenfen Li, Huidong Shi, Bingzhong Xue, Hang Shi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Increasing energy expenditure through activation of brown fat thermogenesis is a promising therapeutic strategy for the treatment of obesity. Epigenetic regulation has emerged as a key player in regulating brown fat development and thermogenic program. Here, we aimed to study the role of DNA methyltransferase 3b (Dnmt3b), a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat function and energy homeostasis. We generated a genetic model with Dnmt3b deletion in brown fat-skeletal lineage precursor cells (3bKO mice) by crossing Dnmt3b-floxed (fl/fl) mice with Myf5-Cre mice. Female 3bKO mice are prone to diet-induced obesity, which is associated with decreased energy expenditure. Dnmt3b deficiency also impairs cold-induced thermogenic program in brown fat. Surprisingly, further RNA-seq analysis reveals a profound up-regulation of myogenic markers in brown fat of 3bKO mice, suggesting a myocyte-like remodeling in brown fat. Further motif enrichment and pyrosequencing analysis suggests myocyte enhancer factor 2C (Mef2c) as a mediator for the myogenic alteration in Dnmt3b-deficient brown fat, as indicated by decreased methylation at its promoter. Our data demonstrate that brown fat Dnmt3b is a key regulator of brown fat development, energy metabolism and obesity in female mice.

Original languageEnglish (US)
Article number1087
JournalBiomolecules
Volume11
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Brown adipocytes
  • Dnmt3b
  • Epigenetics
  • Obesity
  • Thermogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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