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Review
. 2023 Aug 22:10:1190094.
doi: 10.3389/fmolb.2023.1190094. eCollection 2023.

Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases

Harikrishnareddy Paluvai  1   2 , Kumar D Shanmukha  1   2 , Jens Tyedmers  1   2 , Johannes Backs  1   2
Affiliations
Review

Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases

Harikrishnareddy Paluvai et al. Front Mol Biosci. .

Abstract

Histone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. HDAC3 is a class I histone deacetylase that functions as a transcriptional co-repressor, modulating gene expression by removing acetyl groups from histones and non-histone proteins. NCoR1, on the other hand, is a transcriptional co-repressor that interacts with nuclear hormone receptors, including peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor (LXR), to regulate metabolic gene expression. Recent research has revealed a functional link between HDAC3 and NCoR1 in the regulation of metabolic gene expression. Genetic deletion of HDAC3 in mouse models has been shown to improve glucose intolerance and insulin sensitivity in the liver, skeletal muscle, and adipose tissue. Similarly, genetic deletion of NCoR1 has improved insulin resistance and reduced adiposity in mouse models. Dysregulation of this interaction has been associated with the development of cardio-metabolic diseases such as cardiovascular diseases, obesity and type 2 diabetes, suggesting that targeting this pathway may hold promise for the development of novel therapeutic interventions. In this review, we summarize the current understanding of individual functions of HDAC3 and NCoR1/2 and the co-repressor complex formation (HDAC3/NCoR1/2) in different metabolic tissues. Further studies are needed to thoroughly understand the mechanisms through which HDAC3, and NCoR1/2 govern metabolic processes and the implications for treating metabolic diseases.

Keywords: GPS2; HDAC3; NCoR1; PPARs; SMRT.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Classification of HDACs family and their sub cellular localization.
FIGURE 2
FIGURE 2
Co-repressor complex dysregulation in metabolic diseases. The complex formed by HDAC3 and NCoR1/2 reinforces gene repression by acting as a co-repressor. Certain gene promoters are recruited to this complex, leading to reduced gene transcription and metabolic dysfunction.
FIGURE 3
FIGURE 3
High amounts of glucose and insulin phosphorylate NCoR1 by AKT. Phosphorylation of NCoR1 changes its activity from co-repressor to co-activator, thereby activating NRs.
FIGURE 4
FIGURE 4
Phenotypes of HDAC3 and NCoR1 knockout models in different metabolic tissues.
See this image and copyright information in PMC

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