Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
PLoS One. 2023 Oct 20;18(10):e0293217. doi: 10.1371/journal.pone.0293217. eCollection 2023.
Epigenetic modifications, particularly histone acetylation-deacetylation and its related enzymes, such as sirtuin 1 (SIRT1) deacetylase, may have substantial roles in the pathogenesis of obesity and its associated health issues. This study aimed to evaluate global histone acetylation status and SIRT1 gene expression in children and adolescents with obesity and their association with metabolic and anthropometric parameters.
This study included 60 children and adolescents, 30 with obesity and 30 normal-weight. The evaluation consisted of the analysis of global histone acetylation levels and the expression of the SIRT1 gene in peripheral blood mononuclear cells, by specific antibody and real-time PCR, respectively. Additionally, insulin, fasting plasma glucose, lipid profile and tumor necrosis factor α (TNF-α) levels were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic syndrome was determined based on the diagnostic criteria established by IDF.
Individuals with obesity, particularly those with insulin resistance, had significantly higher histone acetylation levels compared to control group. Histone acetylation was positively correlated with obesity indices, TNF-α, insulin, and HOMA-IR. Additionally, a significant decrease in SIRT1 gene expression was found among obese individuals, which was negatively correlated with the histone acetylation level. Furthermore, SIRT1 expression levels showed a negative correlation with various anthropometric and metabolic parameters.
Histone acetylation was enhanced in children and adolescents with obesity, potentially resulting from down-regulation of SIRT1, and could play a role in the obesity-associated metabolic abnormalities and insulin resistance. Targeting global histone acetylation modulation might be considered as an epigenetic approach for early obesity management.
表观遗传修饰，尤其是组蛋白乙酰化-去乙酰化及其相关酶，如沉默调节蛋白 1（SIRT1）去乙酰化酶，可能在肥胖及其相关健康问题的发病机制中发挥重要作用。本研究旨在评估肥胖儿童和青少年的整体组蛋白乙酰化状态和 SIRT1 基因表达及其与代谢和人体测量参数的关系。
本研究纳入 60 名儿童和青少年，30 名肥胖，30 名体重正常。评估包括通过特异性抗体和实时 PCR 分别分析外周血单个核细胞中的整体组蛋白乙酰化水平和 SIRT1 基因的表达。此外，还测量了胰岛素、空腹血糖、血脂谱和肿瘤坏死因子-α（TNF-α）水平。使用稳态模型评估胰岛素抵抗（HOMA-IR）评估胰岛素抵抗。根据 IDF 建立的诊断标准确定代谢综合征。
肥胖个体，特别是存在胰岛素抵抗的个体，其组蛋白乙酰化水平明显高于对照组。组蛋白乙酰化与肥胖指数、TNF-α、胰岛素和 HOMA-IR 呈正相关。此外，肥胖个体的 SIRT1 基因表达显著下降，与组蛋白乙酰化水平呈负相关。此外，SIRT1 表达水平与各种人体测量和代谢参数呈负相关。
肥胖儿童和青少年的组蛋白乙酰化水平升高，可能是由于 SIRT1 下调所致，可能在肥胖相关代谢异常和胰岛素抵抗中发挥作用。靶向整体组蛋白乙酰化调节可能被认为是早期肥胖管理的一种表观遗传方法。
