DNA Methylation in the Hypothalamic Feeding Center and Obesity

Abstract

Obesity rates have been increasing worldwide for decades, mainly due to environmental factors, such as diet, nutrition, and exercise. However, the molecular mechanisms through which environmental factors induce obesity remain unclear. Several mechanisms underlie the body's response to environmental factors, and one of the main mechanisms involves epigenetic modifications, such as DNA methylation. The pattern of DNA methylation is influenced by environmental factors, and altered DNA methylation patterns can affect gene expression profiles and phenotypes. DNA methylation may mediate the development of obesity caused by environmental factors. Similar to the factors governing obesity, DNA methylation is influenced by nutrients and metabolites. Notably, DNA methylation is associated with body size and weight programming. The DNA methylation levels of proopiomelanocortin (Pomc) and neuropeptide Y (Npy) in the hypothalamic feeding center, a key region controlling systemic energy balance, are affected by diet. Conditional knockout mouse studies of epigenetic enzymes have shown that DNA methylation in the hypothalamic feeding center plays an indispensable role in energy homeostasis. In this review, we discuss the role of DNA methylation in the hypothalamic feeding center as a potential mechanism underlying the development of obesity induced by environmental factors.

Keywords: DNA methylation; DNMT3A; Hypothalamus; Obesity.

Figure 1

Metabolic control of DNA methylation. DNA methylation and demethylation are influenced by micronutrients and metabolites. VB6, vitamin B6; ATP, adenosine triphosphate; SAM, S-adenosyl methionine; VB12, vitamin B12; 5mC, 5-methylated cytosine; DNMT, DNA methyltransferase; TET, ten–eleven translocation methylcytosine dioxygenase; C, cytosine; 5hmC, 5-hydroxymethylated cytosine; TCA, tricarboxylic acid; IDH, isocitrate dehydrogenase; AMPK, AMP-activated protein kinase.