JOURNAL ARTICLE
REVIEW

Food intake in early life and epigenetic modifications of pro-opiomelanocortin expression in arcuate nucleus

Sandra Aparecida Benite-Ribeiro, Valkíria Alves de Lima Rodrigues, Mônica Rodrigues Ferreira Machado
Molecular Biology Reports 2021 April 20
33877530
The prevalence of obesity is increasing in nowadays societies and, despite being a multifactorial disease, it has a significant correlation with food intake. The control of food intake is performed by neurons of the arcuate nucleus of the hypothalamus (ARC), which secret orexigenic and anorexigenic neuropeptides, such as proopiomelanocortin (POMC), under stimulation of, e.g., ghrelin, insulin, and leptin. Insulin, uses inositol 1,4,5-trisphosphate/serine-threonine kinase (IP3/Akt) pathways and stimulates the exclusion of (Forkhead box protein O1) FOXO1 from the nucleus and thereby does the inactivation of the inhibition of POMC expression, while Leptin stimulates signal transducer and activator of transcription 3 (STAT3) phosphorylation and POMC expression. Epigenetic modifications of the synthesis of these neuropeptides can lead to an increased caloric intake, which, in turn, is an important risk factor for obesity and its comorbidities. Epigenetic modifications are reversible, so the search for epigenetic targets has significant scientific and therapeutic appeal. In this review, we synthesize the effect of food intake on the epigenetic modifications of Neuropeptide Y and Pro-opiomelanocortin of ARC and its relationships with obesity development and comorbidities. We found that there is no consensus on the methylation of neuropeptides when the evaluations are carried out in different promoters. Based on reports carried on in the early life in laboratory animals, which is the timeline that the vast majority of author used to study this topic, chronic inflammation, defects in insulin and leptin signaling may be linked to changes occurring in the phosphoinositide 3-kinase/Akt (PI3K/Akt) and/or STAT3/SOCS3 (cytokine signaling 3) pathways. In its turn, the epigenetic modifications related to increased food intake and reduced energy expenditure may be associated with PI3K/Akt and STAT3/SOCS3 signaling disruption and Pro-opiomelanocortin expression.

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