Format

Send to

Choose Destination
J Endocrinol. 2018 Aug 18. pii: JOE-18-0173. doi: 10.1530/JOE-18-0173. [Epub ahead of print]

Adipocyte HDAC4 activation leads to beige adipocyte expansion and reduced adiposity.

Author information

1
E Paulo, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
2
D Wu, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
3
P Hecker, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
4
Y Zhang, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
5
B Wang, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, 94158, United States biao.wang@ucsf.edu.

Abstract

Numerous studies have suggested that beige adipocyte abundance is correlated with improved metabolic performance, but direct evidence showing that beige adipocyte expansion protects animals from the development of obesity is missing. Previously, we have described that the Liver kinase b1 (Lkb1) regulates beige adipocyte renaissance in subcutaneous inguinal white adipose tissue (iWAT) through a class IIa histone deacetylase 4 (HDAC4)-dependent mechanism. This study investigates the physiological impact of persistent beige adipocyte renaissance in energy homeostasis in mice. Here we present that the transgenic mice H4-TG, overexpressing constitutively active HDAC4 in adipocytes, showed beige adipocyte expansion in iWAT at room temperature. H4-TG mice exhibited increased energy expenditure due to beige adipocyte expansion. They also exhibited reduced adiposity under both normal chow and high-fat diet (HFD) feeding conditions. Specific ablation of beige adipocytes reversed the protection against HFD-induced obesity in H4-TG mice. Taken together, our results directly demonstrate that beige adipocyte expansion regulates adiposity in mice, and targeting beige adipocyte renaissance may present a novel strategy to tackle obesity in humans.

PMID:
30121575
PMCID:
PMC6379159
[Available on 2020-02-18]
DOI:
10.1530/JOE-18-0173

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center