Chlorogenic Acid Attenuates Hepatic Steatosis by Suppressing ZFP30

• Published in: Journal of agricultural and food chemistry 2024-01, Vol.72 (1), p.245-258
• Main Authors: Ding, Han, Ge, Kunyi, Fan, Changyu, Liu, Dandan, Wu, Chenyu, Li, Rongpeng, Yan, Feng-Juan
• Format: Article
• Language: English
• Subjects: Animals; Bioactive Constituents, Metabolites, and Functions; Chlorogenic Acid - metabolism; Chlorogenic Acid - pharmacology; Diet, High-Fat; Fatty Acids, Nonesterified - metabolism; Humans; Lipid Metabolism; Liver - metabolism; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - metabolism; PPAR alpha - genetics; PPAR alpha - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.3c02988

Nonalcoholic fatty liver disease (NAFLD) has become a major global health problem with no approved pharmacological treatment for this disease. Thus, it is urgent to develop effective therapeutic targets for clinical intervention. Here, we show for the first time that ZFP30, a member of the KRAB-ZFP family, is significantly increased in NAFLD models. ZFP30 silencing ameliorates free fatty acid (FFA)-induced lipid accumulation; in contrast, the ZFP30 overexpression exacerbates the triglyceride accumulation and steatosis in hepatocytes. Further investigation revealed that the effects of ZFP30 on hepatic lipid accumulation were mainly attributed to the PPARα downregulation in the NAFLD model. Mechanistically, ZFP30 directly binded to the promoter of PPARα and recruited KAP1 to suppress its transcription. Moreover, chlorogenic acid (CGA) reversed the upregulation of ZFP30 in NAFLD, promoting the PPARα expression, resulting in enhanced fatty acid oxidation and alleviated hepatic steatosis. Collectively, our study indicates ZFP30 as a potential target for NAFLD treatment.