Department of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan.
Cells. 2022 Nov 24;11(23):3751. doi: 10.3390/cells11233751.
The liver is a crucial organ for maintaining homeostasis in living organisms and is the center of various metabolic functions. Therefore, abnormal metabolic activity, as in metabolic syndrome, leads to pathological conditions, such as abnormal accumulation of lipids in the liver. Inflammation and cell death are induced by several stresses in the fatty liver, namely steatohepatitis. In recent years, an increase in non-alcoholic steatohepatitis (NASH), which is not dependent on excessive alcohol intake, has become an issue as a major cause of liver cirrhosis and liver cancer. There are several recent findings on functional sex-based differences, NASH, and cell stress and death in the liver. In particular, NASH-induced liver injury and tumorigeneses were suppressed by B cell lymphoma 6, the transcriptional factor regulating sex-based liver functional gene expression. In this review, we discuss cell response to stress and lipotoxicity in NASH and its regulatory mechanisms.
肝脏是维持生物体内稳态的关键器官,也是各种代谢功能的中心。因此,代谢综合征等异常代谢活动会导致肝脏中脂质异常积累等病理状况。在脂肪肝中,几种应激会诱导炎症和细胞死亡,即脂肪性肝炎。近年来,非酒精性脂肪性肝炎(NASH)的发病率不断上升,这已成为肝硬化和肝癌的主要原因,而 NASH 并不依赖于过量饮酒。目前有一些关于性别相关差异、NASH 和肝细胞应激及死亡的最新研究结果。特别是,转录因子调节性别相关肝功能基因表达的 B 细胞淋巴瘤 6 可抑制 NASH 诱导的肝损伤和肿瘤发生。在这篇综述中,我们讨论了 NASH 中的细胞应激和脂毒性及其调控机制。