Metabolically healthy obesity (MHO) is a considerably controversial concept as it is considered a transitory condition towards the development of different pathologies (type 2 diabetes, insulin resistance, or cardiovascular disease). MHO is closely related to lifestyle and environmental factors. Epigenetics has become an essential biological tool to analyze the link between obesity and metabolic status. The aim of this study was to determine whether MHO status is conditioned by the DNA methylation (DNAm) of several genes related to lipid metabolism (lipoprotein lipase, retinoid X receptor alpha, liver X receptor, stearoyl-CoA desaturase, sterol regulatory element binding factor 1), and inflammation (LEP) in peripheral blood mononuclear cells (PBMCs) from 131 prepubertal subjects with MHO phenotype after lifestyle modifications with personalized Mediterranean diet (MedDiet) combined with a physical activity (PA) program. The DNAm of all studied genes were significantly modified in the population after 12 months of lifestyle modifications (MedDiet and PA). In addition, associations were found between the DNAm studies and BMI, homeostatic model assessment of insulin resistance, monounsaturated fatty acid and polyunsaturated fatty acid, moderate-vigorous PA, fat mass, and adherence to MedDiet. It was found that DNAm of genes related to lipid metabolism and inflammation are also present in childhood and that this methylation profile can be modified by interventions based on MedDiet and PA.

中文翻译：

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肥胖症的表观遗传学方法：经历生活方式改变的青春期前人群的 DNA 甲基化。

代谢健康肥胖 (MHO) 是一个相当有争议的概念，因为它被认为是导致不同病理（2 型糖尿病、胰岛素抵抗或心血管疾病）发展的暂时性疾病。MHO与生活方式和环境因素密切相关。表观遗传学已成为分析肥胖与代谢状态之间联系的重要生物学工具。本研究的目的是确定 MHO 状态是否由与脂质代谢相关的几个基因（脂蛋白脂肪酶、视黄醇 X 受体 α、肝 X 受体、硬脂酰辅酶 A 去饱和酶、甾醇调节元件结合因子）的 DNA 甲基化 (DNAm) 决定。 1) 以及外周血单核细胞 (PBMC) 中的炎症 (LEP)，这些受试者来自 131 名具有 MHO 表型的青春期前受试者，他们采用个性化地中海饮食 (MedDiet) 结合体力活动 (PA) 计划改变生活方式后。经过 12 个月的生活方式改变（MedDiet 和 PA）后，人群中所有研究基因的 DNAm 均发生显着改变。此外，还发现 DNAm 研究与 BMI、胰岛素抵抗稳态模型评估、单不饱和脂肪酸和多不饱和脂肪酸、中等强度 PA、脂肪量和 MedDiet 依从性之间存在关联。研究发现，与脂质代谢和炎症相关的基因 DNAm 也存在于儿童时期，并且这种甲基化谱可以通过基于 MedDiet 和 PA 的干预措施进行修改。