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Endocrinology. 2018 Jul 1;159(7):2520-2527. doi: 10.1210/en.2018-00257.

HDAC3-Selective Inhibition Activates Brown and Beige Fat Through PRDM16.

Liao J1,2, Jiang J1,3, Jun H1, Qiao X1,4, Emont MP1,5, Kim DI1, Wu J1,5.

Author information

1
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan.
2
Department of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
3
Department of Respiratory Medicine, Key Site of National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
4
Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
5
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.

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.

PMID:
29757434
PMCID:
PMC6456926
DOI:
10.1210/en.2018-00257
[Indexed for MEDLINE]
Free PMC Article

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