Berberine Attenuates Nonalcoholic Hepatic Steatosis by Regulating Lipid Droplet‐Associated Proteins: In Vivo, In Vitro and Molecular Evidence

作者：Hongzhan Wang, Zhi Wang, Dingkun Wang, Kexin Nie, Wenbin Wu, Yang Gao, Chen Shen, Xinyue Jiang, Yueheng Tang, Hao Su, Meilin Hu, Ke Fang, Hui Dong · 发表于：Journal of Cellular and Molecular Medicine · 年份：2025 · DOI：10.1111/jcmm.70524 · 被引用次数：8 · 研究领域：Lipid metabolism and biosynthesis、Liver Disease Diagnosis and Treatment、Diet, Metabolism, and Disease

Hepatic lipid droplet (LD) accumulation is a hallmark of nonalcoholic fatty liver disease (NAFLD). Although the clinical efficacy of berberine (BBR) in treating NAFLD has been established, the mechanism remains uncertain. This study is to evaluate the effects of BBR on hepatic LDs and investigate the underlying mechanisms. Using high-fat diet-induced obese (DIO) mice as the model for NAFLD, BBR was administered daily by gavage for 4 weeks. Liver tissue was examined for changes in lipid deposition and histology. Transcriptomics was performed to screen differently expressed genes. The potential targets of BBR against NAFLD were then determined by Western Blot and immunostaining. In oleic acid (OA)-induced HepG2 cells, the link between BBR and potential targets was further elucidated through the activation or antagonism of PPARα. The binding of BBR to potential targets was predicted using molecular docking. BBR significantly reduced hepatic steatosis by decreasing LD size rather than number. Transcriptomics with validation demonstrated that BBR modulated the expression of LD-associated proteins CIDEA and PLIN4 in the liver. Further investigations revealed that BBR reversed the abnormal elevation of BSCL2 and PLIN2 in steatotic livers. Finally, we found that BBR reduced LD size in OA-induced HepG2 cells by regulating BSCL2 and PPARα-mediated CIDEA/PLIN4/PLIN2. Notably, BBR could bind well to PPARα and BSCL2. BBR can attenuate hepatic steatosis in DIO mice by reducing LD size thro...