Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence

Abstract

Obesity is a chronic metabolic disorder and a growing global public health challenge, affecting hundreds of millions of individuals worldwide. While diet and physical activity are well-established contributors, increasing evidence underscores the critical role of epigenetic mechanisms in mediating obesity-related processes. Epigenetic modifications-such as DNA methylation, RNA methylation (particularly N6-methyladenosine), histone modifications, non-coding RNAs, and chromatin remodeling-modulate gene expression without altering the DNA sequence. This review aims to provide an overview of the epigenetic mechanisms involved in obesity, with an emphasis on their molecular functions and regulatory networks. Integrating findings from relevant studies, we discuss how these modifications influence obesity-related outcomes through regulating key processes such as adipocyte differentiation and energy metabolism. Advancing our understanding of epigenetic regulation may pave the way for novel, targeted strategies in the prevention and treatment of obesity.

Keywords: DNA methylation; RNA methylation; adipogenesis; energy metabolism; epigenetic; histone modifications; obesity.

Figure 1

The role of histone modifications in adipogenesis. PRMT1-mediated H4R3 methylation promotes PPARγ expression and adipogenesis; NSD2-mediated H3K27 methylation suppresses C/EBPα expression and inhibits adipogenesis; PRDM9 methylates H3K4 to activate Prdm16 and Ucp1, thereby enhancing browning and thermogenesis; LSD1, a demethylase, removes H3K9 methylation, facilitating Ucp1 expression; SUV420H2 catalyzes H4K20 methylation, suppressing 4e-bp1 and thereby activating PGC1α, contributing to thermogenic activation and adipogenesis; SIRT1, by deacetylating H3K27 and H3K9, represses C/EBPβ, negatively regulating adipogenesis; AMPK phosphorylates H2B at Ser36, resulting in increased transcription of adipogenesis-related genes. Abbreviations: PRMT1, protein arginine N-methyltransferase 1; NSD2, nuclear receptor-binding SET domain 2; PRDM9, PR domain-containing protein 9; LSD1, lysine-specific demethylase 1; SUV420H2, suppressor of variegation 4-20 homolog 2; SIRT1, silent mating-type information regulation 2 homolog 1; AMPK, AMP-activated protein kinase; PPARγ, peroxisome proliferator-activated receptor γ; C/EBPα, CCAAT/enhancer binding protein α; Prdm16, PR domain-containing protein 16; Ucp1, uncoupling protein 1; 4e-bp1, 4E-binding protein 1; PGC1α, peroxisome proliferator-activated receptor-γ coactivator 1α; C/EBPβ, CCAAT/enhancer-binding protein β.