Tang Sainan, Wu Shanshan, Zhang Wenzhe, Ma Lili, Zuo Li, Wang Hua
Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China.
Laboratory of Molecular Biology, Department of Biochemistry, School of Basic Medical Science, Anhui Medical University, Hefei, 230022, Anhui, China.
Arch Toxicol. 2025 Jan;99(1):127-152. doi: 10.1007/s00204-024-03920-1. Epub 2024 Dec 18.
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are two major chronic liver diseases worldwide. The triggers for fatty liver can be derived from external sources such as adipose tissue, the gut, personal diet, and genetics, or internal sources, including immune cell responses, lipotoxicity, hepatocyte death, mitochondrial dysfunction, and extracellular vesicles. However, their pathogenesis varies to some extent. This review summarizes various immune mechanisms and therapeutic targets associated with these two types of fatty liver disease. It describes the gut-liver axis and adipose tissue-liver crosstalk, as well as the roles of different immune cells (both innate and adaptive immune cells) in fatty liver disease. Additionally, mitochondrial dysfunction, extracellular vesicles, microRNAs (miRNAs), and gastrointestinal hormones are also related to the pathogenesis of fatty liver. Understanding the pathogenesis of fatty liver and corresponding therapeutic strategies provides a new perspective for developing novel treatments for fatty liver disease.
酒精性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）是全球范围内两种主要的慢性肝病。脂肪肝的触发因素可源自外部来源，如脂肪组织、肠道、个人饮食和遗传因素，或内部来源，包括免疫细胞反应、脂毒性、肝细胞死亡、线粒体功能障碍和细胞外囊泡。然而，它们的发病机制在一定程度上有所不同。本综述总结了与这两种类型脂肪肝疾病相关的各种免疫机制和治疗靶点。它描述了肠-肝轴和脂肪组织-肝的相互作用，以及不同免疫细胞（固有免疫细胞和适应性免疫细胞）在脂肪肝疾病中的作用。此外，线粒体功能障碍、细胞外囊泡、微小RNA（miRNA）和胃肠激素也与脂肪肝的发病机制有关。了解脂肪肝的发病机制和相应的治疗策略为开发脂肪肝疾病的新治疗方法提供了新的视角。
