Role of peripheral clock genes in the progression, prevention, and treatment of nonalcoholic steatohepatitis
Journal Title: Journal of Clinical Hepatology - Year 2024, Vol 40, Issue 12
Abstract
As a severe clinical manifestation of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH) is characterized by lipid deposition and inflammatory damage in the liver. At present, clinical medications for NASH are still in the exploratory phase, and it is urgent to make progress. Recent studies have shown that the pathogenesis of NASH is associated with circadian rhythm disorders in the liver, with the specific manifestation of dysregulated expression of liver clock genes such as BMAL1, which increases hepatic lipogenesis, reduces fatty acid oxidation, and activates pro-inflammatory factors. Therefore, improving circadian rhythm of the liver and regulating the expression of liver clock genes are feasible strategies for the prevention and treatment of NASH. Currently, some medications for NASH via activating the proteins encoded by clock genes have been applied in animal experiments, for example, the REVERB full-agonist SR9009 can inhibit the development of liver inflammation, which confirms the possibility of NASH treatment by targeting the proteins encoded by clock genes. This article summarizes the role of hepatic clock genes in regulating lipid metabolism and the development and progression of inflammation in the liver and elaborates on the recent advances in medications targeting clock genes and the proteins encoded by clock genes, in order to provide new targets for the treatment of NASH.
Authors and Affiliations
Siyan LIU, Jingyi TIAN, Yuyang HUANG, Tianqi GU, Mingyue DENG, Pan YANG
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