Ciências Biológicas, Federal University of Jataí (UFJ), Rodovia 364, Km 195, nº 3800, Jataí, Goiás, CEP 75801-615, Brasil.
Pós-Graduação de Ciências Aplicadas À Saúde, Federal University of Jataí (UFJ), Rodovia 364, Km 195, nº 3800, Jataí, Goiás, CEP 75801-615, Brasil.
Mol Biol Rep. 2021 Apr;48(4):3773-3784. doi: 10.1007/s11033-021-06340-x. Epub 2021 Apr 20.
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.
如今，肥胖的患病率正在上升，尽管肥胖是一种多因素疾病，但它与食物摄入有显著的相关性。食物摄入的控制是由下丘脑弓状核（ARC）的神经元完成的，这些神经元在胃饥饿素、胰岛素和瘦素等刺激下分泌食欲肽和厌食肽，如前阿黑皮素原（POMC）。胰岛素利用肌醇 1,4,5-三磷酸/丝氨酸-苏氨酸激酶（IP3/Akt）途径，刺激叉头框蛋白 O1（FOXO1）从核内排出，从而使 POMC 表达的抑制作用失活，而瘦素刺激信号转导和转录激活因子 3（STAT3）磷酸化和 POMC 表达。这些神经肽合成的表观遗传修饰可导致热量摄入增加，而热量摄入增加是肥胖及其合并症的重要危险因素。表观遗传修饰是可逆的，因此寻找表观遗传靶点具有重要的科学和治疗吸引力。在这篇综述中，我们综合了食物摄入对 ARC 中神经肽 Y 和 Pro-opiomelanocortin 的表观遗传修饰及其与肥胖发展和合并症的关系的影响。我们发现，当在不同启动子中进行评估时，神经肽的甲基化没有共识。基于实验室动物早期生命的报告，这是绝大多数作者用于研究这一课题的时间线，慢性炎症、胰岛素和瘦素信号缺陷可能与发生在磷酸肌醇 3-激酶/ Akt（PI3K/Akt）和/或 STAT3/SOCS3（细胞因子信号 3）途径中的变化有关。反过来，与食物摄入增加和能量消耗减少相关的表观遗传修饰可能与 PI3K/Akt 和 STAT3/SOCS3 信号中断和 Pro-opiomelanocortin 表达有关。
