Traslational Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
Mini Rev Med Chem. 2023;23(17):1680-1690. doi: 10.2174/1389557523666230130093512.
Metabolically associated fatty liver disease, formerly called nonalcoholic fatty liver disease, is the most common liver disease globally, representing the third cause of liver transplantation. Metabolically associated fatty liver disease is defined as having more than 5% lipid droplets in hepatocytes without other concomitant liver diseases. Various stimuli such as the secretion of inflammatory cytokines, mitochondrial and endoplasmic reticulum dysfunction due to oxidative stress, alteration of the intestine-liver axis, bacterial dysbiosis, as well as genetic and epigenetic factors can modify the progression of metabolically associated fatty liver disease to fibrosis, cirrhosis, and may reach hepatocellular carcinoma. Epigenetics is responsible for a highly sophisticated regulatory system that controls many cellular processes in response to multiple environmental factors as an adaptive mechanism unrelated to alterations in the primary deoxyribonucleic acid sequence, including gene expression, microRNAs, DNA methylation, modifications in histones, and DNA-protein interactions. Several studies have shown that epigenetic changes are associated with various diseases, including metabolically associated fatty liver disease. Nutri epigenomics is the interaction between nutrition and components at the transcriptional or post-transcriptional level. Methylation processes involve micronutrients that regulate epigenetic states in a physiological and pathological context. Micronutrients such as methionine, folate, and choline are the main components of one-carbon metabolism, functioning as methyl group donors, and their deficiency predisposes to various pathologies such as metabolically associated fatty liver disease. Understanding of epigenetic modifiers leads us to develop new therapeutic therapies for patients with metabolically associated fatty liver disease.
代谢相关脂肪性肝病，以前称为非酒精性脂肪性肝病，是全球最常见的肝病，是肝移植的第三大病因。代谢相关脂肪性肝病的定义为肝细胞中存在超过 5%的脂滴，而没有其他伴随的肝病。各种刺激因素，如炎症细胞因子的分泌、氧化应激引起的线粒体和内质网功能障碍、肠-肝轴的改变、细菌失调以及遗传和表观遗传因素，都可以改变代谢相关脂肪性肝病向纤维化、肝硬化的进展，并可能发展为肝细胞癌。表观遗传学负责一个高度复杂的调控系统，该系统可以控制许多细胞过程，以响应多种环境因素作为一种与主要脱氧核糖核酸序列改变无关的适应机制，包括基因表达、微小 RNA、DNA 甲基化、组蛋白修饰和 DNA-蛋白质相互作用。许多研究表明，表观遗传变化与包括代谢相关脂肪性肝病在内的各种疾病有关。营养表观基因组学是营养与转录或转录后水平的成分之间的相互作用。甲基化过程涉及调节生理和病理环境中表观遗传状态的微量营养素。微量营养素，如蛋氨酸、叶酸和胆碱，是一碳代谢的主要成分，作为甲基供体发挥作用，它们的缺乏易导致各种病理状态，如代谢相关脂肪性肝病。对表观遗传修饰物的理解使我们能够为代谢相关脂肪性肝病患者开发新的治疗方法。
