Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece.
Department of Gastroenterology, General Hospital of Patras, 26332 Patras, Greece.
Int J Mol Sci. 2023 Aug 16;24(16):12864. doi: 10.3390/ijms241612864.
Nonalcoholic fatty liver disease (NAFLD), the most prominent cause of chronic liver disease worldwide, is a rapidly growing epidemic. It consists of a wide range of liver diseases, from steatosis to nonalcoholic steatohepatitis, and predisposes patients to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. NAFLD is strongly correlated with obesity; however, it has been extensively reported among lean/nonobese individuals in recent years. Although lean patients demonstrate a lower prevalence of diabetes mellitus, central obesity, dyslipidemia, hypertension, and metabolic syndrome, a percentage of these patients may develop steatohepatitis, advanced liver fibrosis, and cardiovascular disease, and have increased all-cause mortality. The pathophysiological mechanisms of lean NAFLD remain vague. Studies have reported that lean NAFLD demonstrates a close association with environmental factors, genetic predisposition, and epigenetic modifications. In this review, we aim to discuss and summarize the epigenetic mechanisms involved in lean NAFLD and to introduce the interaction between epigenetic patterns and genetic or non genetic factors. Several epigenetic mechanisms have been implicated in the regulation of lean NAFLD. These include DNA methylation, histone modifications, and noncoding-RNA-mediated gene regulation. Epigenetics is an area of special interest in the setting of lean NAFLD as it could provide new insights into the therapeutic options and noninvasive biomarkers that target this under-recognized and challenging disorder.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病病因，呈迅速流行趋势。它由一系列广泛的肝脏疾病组成，从单纯性脂肪变性到非酒精性脂肪性肝炎，可使患者易患肝纤维化、肝硬化，甚至肝细胞癌。NAFLD 与肥胖密切相关；然而，近年来在瘦/非肥胖个体中已广泛报道。尽管瘦型患者的糖尿病、中心性肥胖、血脂异常、高血压和代谢综合征的患病率较低，但这些患者中仍有一定比例可能发展为脂肪性肝炎、晚期肝纤维化和心血管疾病，并导致全因死亡率增加。瘦型 NAFLD 的病理生理机制尚不清楚。研究表明，瘦型 NAFLD 与环境因素、遗传易感性和表观遗传修饰密切相关。在这篇综述中，我们旨在讨论和总结瘦型 NAFLD 涉及的表观遗传机制，并介绍表观遗传模式与遗传或非遗传因素之间的相互作用。几种表观遗传机制被认为与瘦型 NAFLD 的调控有关。这些机制包括 DNA 甲基化、组蛋白修饰和非编码 RNA 介导的基因调控。在瘦型 NAFLD 中，表观遗传学是一个特别关注的领域，因为它可以为这一未被充分认识且具有挑战性的疾病提供新的治疗选择和非侵入性生物标志物的见解。
