Department of Physiology & Biophysics, National Defense Medical Center, Taipei, 114, Taiwan.
Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan.
Cell Death Dis. 2021 Mar 26;12(4):323. doi: 10.1038/s41419-021-03608-9.
In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.
在肥胖成年人中，非酒精性脂肪性肝病 (NAFLD) 伴随着多种代谢功能紊乱。尽管肝内脂肪酸合成增加已被确定为 NAFLD 发展的关键介质，但潜在机制仍有待阐明。在这项研究中，我们报道了与淋巴细胞无反应性相关的基因（GRAIL）在肝脂肪变性的人类和小鼠肝脏中的表达上调。Grail 缺失显著减轻了高脂肪饮食诱导的肝脏脂肪堆积和与脂质代谢相关基因的表达，无论是在体外还是在体内。相反，GRAIL 的过表达在小鼠和肝细胞中加剧了脂质堆积并增强了脂质代谢基因的表达。我们的结果表明，Grail 通过与 Sirtuin 1 相互作用来调节肝脂肪变性中的脂质积累。因此，Grail 是 NAFLD 发展过程中的一个重要分子调节剂。
