BET bromodomain inhibition suppresses adipogenesis in mice

Qiong Duan1,2, Pei Wu3, Zhenzhen Liu3

  • 1Department of Cardiology, The First Affiliated Hospital of Nanchang University, Yongwaizheng Street, Nanchang, China. qiongduan@csu.edu.cn.

Endocrine
|November 7, 2019
PubMed
Abstract

Insights

BET bromodomain inhibition suppresses adipogenesis in vivo. This study shows that inhibiting BET bromodomain reduces body weight gain and impairs adipose tissue function in mice.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • BET bromodomain proteins are epigenetic regulators implicated in gene transcription.
  • Previous in vitro studies demonstrated that BET bromodomain inhibition suppresses adipogenesis.

Purpose of the Study:

  • To investigate the in vivo effects of BET bromodomain inhibition on adipogenesis.
  • To determine if targeting BET bromodomains can suppress fat accumulation and modulate adipose tissue function in a mouse model.

Main Methods:

  • Generation of Brd4 conditional knockout mice (Brd4fl/+/Fabp4-cre).
  • Treatment of mice with a high-fat diet (HFD) and administration of JQ1, a BET bromodomain inhibitor.
  • Assessment of body weight, body composition via dual-energy X-ray absorptiometry, and brown adipose tissue characteristics.

Main Results:

  • Partial deletion of Brd4 resulted in lower body weight.
  • JQ1 treatment significantly suppressed body weight gain and reduced white adipose tissue depots.
  • JQ1 treatment decreased brown adipose tissue size and impaired its thermogenic capacity.

Conclusions:

  • BET bromodomain inhibition effectively suppresses adipogenesis in vivo.
  • Targeting BET bromodomains represents a potential therapeutic strategy for obesity and related metabolic disorders.