Role of EZH2 in adipogenesis and obesity: Current state of the art and implications – A review

Abstract

Obesity is characterized by excessive accumulation of adiposity and has been implicated in a strong predisposition to metabolic disorders and cancer, constituting one of the major public health issues worldwide. The formation of new mature adipocytes through differentiation of progenitor or precursor cells during adipogenesis can lead to the expansion of adipose tissue. Recent studies have revealed that the intrinsic risk of obesity arises not only through genetic variants but also through epigenetic predisposition. Enhancer of zeste homolog 2 (EZH2) is an enzymatic catalytic component of polycomb repressive complex 2 that acts as an epigenetic modulator in the regulation of gene expression. EZH2 can modulate the expression of its target genes by the trimethylation of Lys-27 in histone 3 or methylation of non-histone proteins. Emerging evidence has shown the important role played by EZH2 in adipogenesis and obesity. This review provides the latest knowledge about the involvement of EZH2 in the process of adipogenesis and obesity involving adipocyte differentiation, extract key concepts, and highlight open questions toward a better understanding of EZH2 function and the molecular mechanisms underlying obesity.Abbreviations: BMP2 = bone morphogenetic protein 2, C/EBPβ = binding proteins CCAAT/enhancer β, EZH2 = enhancer of zeste homolog 2, GSK-3b = glycogen synthase kinase-3b, H3K27me3 = trimethylation of Lys-27 in histone 3, HOPX = homeodomain-only protein homeobox, PcGs = polycomb group genes, PPARγ = peroxisome proliferator-activated receptor-γ, PRC2 = polycomb repressive complex 2, UTR = untranslated region.

The Regulatory Role of MicroRNAs in Obesity and Obesity-Derived Ailments

“…Furthermore, EZH2 was identified as the main target of miR-138-5p. EZH2 is a polycomb-group protein that is involved in suppressing gene transcription [52]. The expression of EZH2 was high in adipocytes from obese patients, which also had an increased expression of circSAMD4A.…”