Recent progress in epigenetics of obesity

Abstract

Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual's risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.

Keywords: DNA methylation; Epigenetics; Histone modification; Obesity; miRNA.

Fig. 1

Transgenerational transmission of inherited epigenetic changes. It generally involves exposure of F1 gametes in utero to maternal experience (F0), which subsequently affects F2 offspring, and then transmission of the epigenetic characteristics of F3 offspring via unexposed F2 gametes

Fig. 2

The main mechanisms involved in epigenetic regulation

Fig. 3

Diagram showing the mechanism of DNA methylation (DNAm). DNAm often takes place at the 5-carbon location of the cytosine (C) base, mainly in the CG position (CpG loci), which are unevenly allocated throughout the genome and to a lesser extent in non-CG context. Several DNA methyltransferases (DNMTs) are responsible for ligating methyl groups to DNA. The methyl donor is S-adenosylmethionine (SAM). SAM is converted to S-adenosylhomocysteine (SAH)

Fig. 4

DNA methylation (DNAm) in different biological specimens of obesity. The figure illustrates tissues and genes with observed alterations in DNAm in subjects with obesity. Some of these genes are also associated with differential gene expression. Changes in DNAm are more often in obese individuals than in non-obese participants. The full name of the abbreviations can be found in the abbreviate table

Fig. 5

The simplified diagram of histone modification. The histone octamer “bead” was surrounded by a DNA strand and methylated at lysine-9, this kind of modification was often found at promoter regions of silenced genes

Fig. 6

Dysregulation of obesity-associated miRNAs in different biological specimens. It includes blood sample and vascular, heart, and adipose tissues