Department of Life, Health and Environmental Sciences-MESVA, School of Emergency-Urgency Medicine, University of L'Aquila, 67100 L'Aquila, Italy.
F. Balsano Foundation, Via Giovanni Battista Martini 6, 00198 Rome, Italy.
Nutrients. 2023 Nov 12;15(22):4757. doi: 10.3390/nu15224757.
Metabolic dysfunction-associated steatotic fatty liver disease (MASLD), a novel definition for NAFLD, represents one of the most common causes of liver disease, and its incidence is increasing worldwide. It is characterized by a complex etiopathogenesis in which mitochondrial dysfunction exerts a pivotal role together with alteration of lipid metabolism, inflammation, and oxidative stress. Nutrients and bioactive compounds can influence such mechanisms so that changes in diet and lifestyle are regarded as important treatment strategies. Notably, natural compounds can exert their influence through changes of the epigenetic landscape, overall resulting in rewiring of molecular networks involved in cell and tissue homeostasis. Considering such information, the present review aims at providing evidence of epigenetic modifications occurring at mitochondria in response to natural and bioactive compounds in the context of liver (dys)function. For this purpose, recent studies reporting effects of compounds on mitochondria in the context of NAFLD/MASLD, as well as research showing alteration of DNA methylation and non-coding RNAs-related circuits occurring at liver mitochondria, will be illustrated. Overall, the present review will highlight the importance of understanding the bioactive compounds-dependent epigenetic modulation of mitochondria for improving the knowledge of MASLD and identifying biomarkers to be employed for effective preventative strategies or treatment protocols.
代谢相关脂肪性肝病（MAFLD）是一种新型的非酒精性脂肪性肝病定义，代表了最常见的肝脏疾病病因之一，且其发病率在全球范围内呈上升趋势。其特征是发病机制复杂，其中线粒体功能障碍与脂质代谢、炎症和氧化应激的改变一起起着关键作用。营养物质和生物活性化合物可以影响这些机制，因此饮食和生活方式的改变被认为是重要的治疗策略。值得注意的是，天然化合物可以通过改变表观遗传景观来发挥其影响，从而导致参与细胞和组织稳态的分子网络重新布线。考虑到这些信息，本综述旨在提供与肝脏（功能）障碍相关的天然和生物活性化合物作用于线粒体时发生的表观遗传修饰的证据。为此，将举例说明最近报道的在非酒精性脂肪性肝病/代谢相关脂肪性肝病背景下化合物对线粒体影响的研究，以及显示在肝线粒体中发生的 DNA 甲基化和非编码 RNA 相关电路改变的研究。总体而言，本综述将强调理解生物活性化合物对线粒体的表观遗传调节对改善 MAFLD 知识和识别用于有效预防策略或治疗方案的生物标志物的重要性。
