Khusainova Rita, Minniakhmetov Ildar, Vasyukova Olga, Yalaev Bulat, Salakhov Ramil, Kopytina Darya, Guseinova Raisat, Dobreva Ekaterina, Melnichenko Galina, Dedov Ivan, Mokrysheva Natalia
Genomic Medicine Laboratory, Endocrinology Research Centre, Moscow, Russia.
J Obes. 2025 Jul 11;2025:9186826. doi: 10.1155/jobe/9186826. eCollection 2025.
Obesity is a chronic metabolic disease characterized by excessive accumulation or uneven distribution of fat in the body, which poses a serious threat to health. Obesity significantly increases the risk of developing сonditions such as type 2 diabetes, coronary heart disease, hypertension, obstructive sleep apnea, and some types of cancer. The prevalence of obesity, especially in childhood, has increased significantly worldwide over the past few decades. The World Health Organization predicts that 250 million children and adolescents aged 5-19 years will be obese by 2030, which indicates a global problem with far-reaching consequences. Advances in genomic technologies have led to the identification of multiple genetic loci associated with the disease ranging from severe cases with early onset to common multifactorial polygenic forms. Epigenetic changes driven by dietary and lifestyle factors are now recognized as crucial contributors to obesity. These modifications can alter gene expression and thereby link environmental influences to the observable clinical features of the disease. Significant progress has been made in deciphering the genetic architecture of obesity, particularly in pediatric populations. However, further advancement requires integrative multiomics analyses that encompass genomic, epigenomic, transcriptomic, proteomic, metabolomic, and microbiome data. To better understand the complex molecular underpinnings and clinical variability of obesity, researchers are increasingly applying methods from machine learning and artificial intelligence. These technologies help analyze large-scale genomic and phenotypic datasets, allowing for the identification of biological pathways involved in weight regulation. In the future, this may support the design of individualized diagnostic tools and targeted treatment plans that reflect a patient's genetic profile, lifestyle, and environmental exposures. To implement the principles of personalized and precision medicine in the treatment of obesity, it is crucial to identify risk profiles by assessing multiple contributing factors. This approach not only enables the prediction of an individual's risk of obesity and its associated diseases but also facilitates the optimization of treatment based on the patient's genetic profile. This study provides a comprehensive overview of the current understanding of childhood obesity, including its prevalence, genetic determinants, and pathophysiological mechanisms. It highlights the contribution of genetic factors to hereditary and syndromic forms, the role of gene-environment interactions (including nutrition and environmental pollutants), and the influence of epigenetic modifications on metabolic disturbances associated with polygenic obesity.
肥胖是一种慢性代谢性疾病,其特征是体内脂肪过度堆积或分布不均,对健康构成严重威胁。肥胖显著增加了患2型糖尿病、冠心病、高血压、阻塞性睡眠呼吸暂停以及某些类型癌症等疾病的风险。在过去几十年里,肥胖的患病率在全球范围内显著上升,尤其是在儿童时期。世界卫生组织预测,到2030年,全球将有2.5亿5至19岁的儿童和青少年肥胖,这表明肥胖是一个具有深远影响的全球性问题。基因组技术的进步已导致识别出多个与该疾病相关的基因位点,范围从早发性重症病例到常见的多因素多基因形式。由饮食和生活方式因素驱动的表观遗传变化现在被认为是肥胖的关键促成因素。这些修饰可以改变基因表达,从而将环境影响与该疾病可观察到的临床特征联系起来。在解读肥胖的遗传结构方面已经取得了重大进展,特别是在儿科人群中。然而,进一步的进展需要整合多组学分析,包括基因组、表观基因组、转录组、蛋白质组、代谢组和微生物组数据。为了更好地理解肥胖复杂的分子基础和临床变异性,研究人员越来越多地应用机器学习和人工智能方法。这些技术有助于分析大规模的基因组和表型数据集,从而识别参与体重调节的生物途径。未来,这可能有助于设计反映患者基因特征、生活方式和环境暴露情况的个性化诊断工具和靶向治疗方案。为了在肥胖治疗中贯彻个性化和精准医学的原则,通过评估多个促成因素来识别风险特征至关重要。这种方法不仅能够预测个体患肥胖症及其相关疾病的风险,还有助于根据患者的基因特征优化治疗方案。本研究全面概述了目前对儿童肥胖的认识,包括其患病率、遗传决定因素和病理生理机制。它强调了遗传因素对遗传性和综合征性肥胖形式的贡献、基因 - 环境相互作用(包括营养和环境污染物)的作用以及表观遗传修饰对与多基因肥胖相关的代谢紊乱的影响。