期刊
HEPATOLOGY
卷 75, 期 1, 页码 140-153出版社
WILEY
DOI: 10.1002/hep.32148
关键词
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资金
- National Natural Science Foundation of China [81673468, 82003788, 82073280]
- National Key New Drug Innovation Program
- Ministry of Science and Technology of China [2018ZX09201017-006]
- Scientific Startup Foundation for High Level Scientists of China Pharmaceutical University [3154070026]
- Natural Science Foundation of Jiangsu province [BK20190801]
- Youth Project of Natural Science Foundation of Nanjing University of Chinese Medicine [NZY82003788]
- Double First-Class University Project [CPU2018GF10, CPU2018GY46]
This study found elevated levels of ACSL4 in the livers of NAFLD patients, inhibition of which can reduce lipid accumulation. Abemaciclib, a selective ACSL4 inhibitor, shows promise as a potential therapeutic approach for NAFLD.
Background and Aims Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. Approach and Results In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate beta-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Conclusions Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.
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