ESPE Abstracts

Introduction: Widespread changes occur in gene expression in obesity, contributing to metabolic and inflammatory abnormalities. Epigenetic mechanisms play a role in obesity by altering gene expression patterns, and connecting environmental factors to genetic alterations. Histone acetylation is a crucial epigenetic modification that impacts chromatin structure and regulates gene expression. Adipogenesis has been associated with gene-specific increases in histones H3 and H4 acetylation. A link between inflammation and histone modification has also been suggested. SIRT1, an enzyme involved in metabolic regulation, participates in histone deacetylation. This study aimed to investigate global histone acetylation in peripheral blood mononuclear cells (PBMCs) of children and adolescents with obesity, and its correlation with metabolic and inflammatory parameters.

Methods: The study included 60 children and adolescents, aged 11.3±2.3 years, comprising 30 subjects with obesity and 30 healthy controls. Detailed examinations were conducted, and anthropometric characteristics were recorded. Colorimetric methods were used to measure fasting plasma glucose (FPG) and lipid profile. Enzyme-linked immunosorbent assay (ELISA) was employed to assess insulin and TNF-α levels. PBMCs were isolated from fresh blood samples, and DNA and RNA were extracted. SIRT1 gene expression was measured using real-time PCR after preparing cDNA from RNA. Global histone acetylation was evaluated using an ELISA-based method with a specific antibody against acetylated H3 histone. Insulin resistance was determined by homeostatic model assessment of insulin resistance (HOMA-IR), and metabolic syndrome (MetS) was identified based on IDF criteria.

Results: anthropometric parameters, including weight z-score, BMI z-score, waist circumference, and blood pressure, were significantly higher in cases compared to controls. Additionally, glycaemic indices such as FPG, insulin, and HOMA-IR were significantly elevated in children with obesity. Histone acetylation was significantly higher in cases than in controls, and it was also remarkably increased in those with insulin resistance. SIRT1 gene expression was significantly reduced in children with obesity compared to the control group, and a marked inverse correlation was observed between histone acetylation and SIRT1 gene expression. Subjects with obesity also exhibited significantly higher TNF-α concentrations, which were positively correlated with the levels of histone acetylation. In summary we showed for the first time that obesity in children and adolescents is accompanied by increased global histone acetylation, which is associated with insulin resistance and inflammation. Therefore, modulation of histone acetylation may be a potential interventional target for prevention of metabolic abnormalities associated with obesity.