The role of epigenetics in hypothalamic energy balance control: implications for obesity - PubMed (original) (raw)

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The role of epigenetics in hypothalamic energy balance control: implications for obesity

Arnaud Obri et al. Cell Stress. 2019.

Abstract

Despite enormous social and scientific efforts, obesity rates continue to increase worldwide. While genetic factors contribute to obesity development, genetics alone cannot explain the current epidemic. Obesity is essentially the consequence of complex genetic-environmental interactions. Evidence suggests that contemporary lifestyles trigger epigenetic changes, which can dysregulate energy balance and thus contribute to obesity. The hypothalamus plays a pivotal role in the regulation of body weight, through a sophisticated network of neuronal systems. Alterations in the activity of these neuronal pathways have been implicated in the pathophysiology of obesity. Here, we review the current knowledge on the central control of energy balance with a focus on recent studies linking epigenetic mechanisms in the hypothalamus to the development of obesity and metabolic disorders.

Keywords: AgRP neurons; POMC neurons; energy balance; epigenetic; hypothalamus; obesity.

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Conflict of interest statement

Conflict of interest: The authors declare no competing interests.

Figures

Figure 1

Figure 1. FIGURE 1: Obesity is at the interplay between genetic and environmental factors.

The development of obesity is influenced by genetic and environmental factors. The study of monogenic obesity has led the discovery of several obesity susceptibility genes such as Proopimelanocortin (POMC), Melanocortin receptor 4 (MC4R) or Leptin (LEP) among others. However, diverse environmental factors such as the diet, combined with genetic variations, also influence energy balance control.

Figure 2

Figure 2. FIGURE 2: Metabolites influence chromatin architecture.

Glucose and fatty acid catabolism produce acetyl-CoA through metabolic pathways including tricarboxylic acid cycle (TCA) and β-oxidation. Acetyl-CoA regulates histone acetylation because it is important for the enzymatic activity of histone acetyltransferases. NAD+ is produced by oxidative pathways and is a relevant cofactor for histone deacetylation mediated by sirtuins. The methionine cycle is the principal producer of S-adenosyl methionine (SAM), which is a cofactor for histone/DNA methyltransferase (HMT or DNMT). Histone deacetylase (HDAC), ten-eleven translocation (TET), histone demethylase (HDM).

Figure 3

Figure 3. FIGURE 3: Hypothalamic miRNAs control energy balance.

POMC and AgRP neurons from the arcuate nucleus (ARC) send projections to the paraventricular nucleus (PVN) to control energy balance. Dicer and several miRNAs, such as miR-103 and miR-200a, have been proposed to control appetite and body weight likely via POMC neurons. Additionally, miRNA biogenesis is also important for the development of POMC neurons. Melanocortin receptor 4 (MC4R).

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