Nascè Alberto, Gariani Karim, Jornayvaz François R, Szanto Ildiko
Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
Department of Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Antioxidants (Basel). 2022 Jun 9;11(6):1131. doi: 10.3390/antiox11061131.
Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in hepatocytes, is closely linked to insulin resistance and is the most frequent complication of type 2 diabetes mellitus (T2DM). One of the features connecting NAFLD, insulin resistance and T2DM is cellular oxidative stress. Oxidative stress refers to a redox imbalance due to an inequity between the capacity of production and the elimination of reactive oxygen species (ROS). One of the major cellular ROS sources is NADPH oxidase enzymes (NOX-es). In physiological conditions, NOX-es produce ROS purposefully in a timely and spatially regulated manner and are crucial regulators of various cellular events linked to metabolism, receptor signal transmission, proliferation and apoptosis. In contrast, dysregulated NOX-derived ROS production is related to the onset of diverse pathologies. This review provides a synopsis of current knowledge concerning NOX enzymes as connective elements between NAFLD, insulin resistance and T2DM and weighs their potential relevance as pharmacological targets to alleviate fatty liver disease.
非酒精性脂肪性肝病（NAFLD）以肝细胞内异位脂肪堆积为特征，与胰岛素抵抗密切相关，是2型糖尿病（T2DM）最常见的并发症。连接NAFLD、胰岛素抵抗和T2DM的特征之一是细胞氧化应激。氧化应激是指由于活性氧（ROS）产生能力与消除能力之间的不平衡导致的氧化还原失衡。主要的细胞ROS来源之一是NADPH氧化酶（NOX）。在生理条件下，NOX以适时和空间调节的方式有目的地产生ROS，并且是与代谢、受体信号转导、增殖和凋亡相关的各种细胞事件的关键调节因子。相反，NOX衍生的ROS产生失调与多种疾病的发生有关。本综述概述了关于NOX酶作为NAFLD、胰岛素抵抗和T2DM之间连接要素的当前知识，并权衡了它们作为减轻脂肪肝疾病的药理学靶点的潜在相关性。
