Centre for Molecular Medicine and diagnostic (CoMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, India.
Central Research Laboratory, Meenakhsi Ammal Dental College and Hospitals, Academy of Higher Education and Research, Chennai, 600 095, India.
J Nutr Biochem. 2022 Sep;107:109037. doi: 10.1016/j.jnutbio.2022.109037. Epub 2022 May 6.
Modern lifestyle, genetics, nutritional overload through high-fat diet attributed prevalence and diabetes outcomes with various complications primarily due to obesity in which energy-dense diets frequently affect metabolic health. One possible issue usually associated with elevated chronic fat intake is insulin resistance, and hyperglycemia constitutes an important function in altering the carbohydrates and lipids metabolism. Similarly, in assessing human susceptibility to weight gain and obesity, genetic variations play a central role, contributing to keen interest in identifying the possible role of epigenetics as a mediator of gene-environmental interactions influencing the production of type 2 diabetes mellitus and its related concerns. Epigenetic modifications associated with the acceptance of a sedentary lifestyle and environmental stress factors in response to energy intake and expenditure imbalances complement genetic alterations and lead to the production and advancement of metabolic disorders such as diabetes and obesity. Methylation of DNA, histone modifications, and increases in the expression of non-coding RNAs can result in reduced transcriptional activity of key β-cell genes thus creating insulin resistance. Epigenetics contribute to changes in the expression of the underlying insulin resistance and insufficiency gene networks, along with low-grade obesity-related inflammation, increased ROS generation, and DNA damage in multiorgans. This review focused on epigenetic mechanisms and metabolic regulations associated with high-fat diet (HFD)-induced diabetes mellitus.
现代生活方式、遗传学、高脂肪饮食导致的营养过剩与各种并发症的流行都与糖尿病有关，主要原因是肥胖，而高热量饮食经常会影响代谢健康。通常与慢性高脂肪摄入升高相关的一个问题是胰岛素抵抗，高血糖在改变碳水化合物和脂质代谢方面构成了重要功能。同样，在评估人类对体重增加和肥胖的易感性时，遗传变异起着核心作用，这使得人们对确定表观遗传学作为一种调节基因-环境相互作用的中介物以影响 2 型糖尿病及其相关问题的可能作用产生了浓厚兴趣。与接受久坐不动的生活方式和环境应激因素相关的表观遗传修饰，以及对能量摄入和消耗失衡的反应，补充了遗传改变，并导致代谢紊乱的产生和发展，如糖尿病和肥胖。DNA 的甲基化、组蛋白修饰以及非编码 RNA 的表达增加，可能导致关键β细胞基因的转录活性降低，从而导致胰岛素抵抗。表观遗传学导致潜在的胰岛素抵抗和不足基因网络的表达发生变化，以及与低度肥胖相关的炎症、ROS 生成增加和多器官的 DNA 损伤。本综述重点介绍了与高脂肪饮食（HFD）诱导的糖尿病相关的表观遗传机制和代谢调节。
