HDAC3-Selective Inhibition Activates Brown and Beige Fat Through PRDM16

Endocrinology
Jiling LiaoJun Wu

Abstract

It has been reported that class I histone deacetylase (HDAC) inhibition increases thermogenesis in fat, but adipocyte-specific Hdac3 deletions have presented inconsistent results. In this study, we observed that HDAC3 protein levels were lower in brown fat compared with inguinal subcutaneous adipose tissue, and they decreased in both fat depots upon cold exposure. PR domain-containing 16 (PRDM16) physically interacted with HDAC3, and treatment with HDAC3-selective inhibitor RGFP966 induced thermogenic gene expression in murine and human fat cultures. This induction was blunted in the absence of PRDM16. Our results provide evidence that HDAC3 is involved in thermogenesis, suggesting selective inhibition of HDAC3 in brown and beige fat might hold therapeutic potential for counteracting human obesity and metabolic disorders.

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Citations

Jul 18, 2019·BioMed Research International·Ting GuChong Wang
Aug 12, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hanbing LiLinghuan Li
Nov 17, 2020·Frontiers in Genetics·Shaza AsifKyoung-Han Kim
Feb 26, 2021·The Journal of Biological Chemistry·Jin-Seon YookSoonkyu Chung
Jul 2, 2020·Journal of Medicinal Chemistry·Terence C S HoA Ganesan

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