Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Trends Pharmacol Sci. 2021 Mar;42(3):183-190. doi: 10.1016/j.tips.2020.12.001. Epub 2021 Jan 16.
End-stage liver disease (ESLD) is a rare but often fatal complication of nonalcoholic fatty liver disease (NAFLD). In NAFLD, insulin resistance, which is clinically defined as the impairment of insulin's ability to maintain glucose homeostasis, is associated with perturbations in insulin action that promote triglyceride accumulation, such as increasing de novo lipogenesis. However, the key step in the development of ESLD is not the accumulation of triglycerides, but hepatocyte injury. Whether and how triglycerides promote hepatocyte injury remains unclear. Consequently, it is difficult to predict whether drugs designed to reduce hepatic triglycerides will prevent the most important complications of NAFLD.
终末期肝病(ESLD)是一种罕见但通常致命的非酒精性脂肪性肝病(NAFLD)并发症。在 NAFLD 中,胰岛素抵抗,即临床上定义为胰岛素维持血糖稳态的能力受损,与促进甘油三酯积累的胰岛素作用改变有关,如增加从头合成。然而,ESLD 发展的关键步骤不是甘油三酯的积累,而是肝细胞损伤。甘油三酯是否以及如何促进肝细胞损伤尚不清楚。因此,很难预测旨在降低肝内甘油三酯的药物是否会预防 NAFLD 的最重要并发症。