{"title":"Linarin alleviates high-fat diet-induced NAFLD via modulating the PI3K/Akt/mTOR pathway, autophagy, and gut microbiota.","authors":"Mengfan Lv, Yaxin Zhai, Hao Yu, Jiaqi Cheng, Yunfei Wei, Yibo Zhang, Yanmin Zhang, Haihua Feng","doi":"10.1016/j.bbalip.2025.159666","DOIUrl":null,"url":null,"abstract":"<p><p>Linarin (Lin) is a flavonoid compound widely found in traditional herbal medicines and is recognized for its diverse biological properties, including anti-inflammatory, analgesic, antioxidant, hepatoprotective, and anti-apoptotic effects. Non-alcoholic fatty liver disease (NAFLD) is closely associated with autophagy and inflammation processes. However, the interaction between Lin and NAFLD remains underexplored. This study aimed to investigate the protective effects of Lin against NAFLD and its underlying pharmacological mechanisms. In vitro, we established a NAFLD model using AML12 cells stimulated with oleic acid (OA) and palmitic acid (PA). In vivo, we induced a chronic model in mice by feeding them a high-fat diet (HFD). Lipid metabolism markers, Oil Red O staining, and H&E staining were used to assess intracellular lipid accumulation. Inflammatory and autophagic markers were also measured. The 16S rRNA analysis was performed to evaluate the changes in the gut microbiota composition after Lin intervention in mice. Both in vitro and in vivo experiments demonstrated that Lin reduces lipid accumulation, which is mediated through the enhancement of autophagy and the inhibition of the release of inflammatory factors. 16S rRNA analysis revealed that Lin alleviates gut dysbiosis by reducing Firmicutes and Bacteroidetes phyla while increasing the abundance of Akkermansia and Bifidobacterium genera. Mechanistically, Lin activates autophagy via the PI3K/Akt/mTOR pathway, thereby alleviating lipid accumulation and inflammation. These findings suggest that Lin can mitigate NAFLD by inhibiting the activation of the PI3K/Akt/mTOR pathway, highlighting its potential as a promising therapeutic approach for NAFLD.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159666"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular and cell biology of lipids","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.bbalip.2025.159666","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Linarin (Lin) is a flavonoid compound widely found in traditional herbal medicines and is recognized for its diverse biological properties, including anti-inflammatory, analgesic, antioxidant, hepatoprotective, and anti-apoptotic effects. Non-alcoholic fatty liver disease (NAFLD) is closely associated with autophagy and inflammation processes. However, the interaction between Lin and NAFLD remains underexplored. This study aimed to investigate the protective effects of Lin against NAFLD and its underlying pharmacological mechanisms. In vitro, we established a NAFLD model using AML12 cells stimulated with oleic acid (OA) and palmitic acid (PA). In vivo, we induced a chronic model in mice by feeding them a high-fat diet (HFD). Lipid metabolism markers, Oil Red O staining, and H&E staining were used to assess intracellular lipid accumulation. Inflammatory and autophagic markers were also measured. The 16S rRNA analysis was performed to evaluate the changes in the gut microbiota composition after Lin intervention in mice. Both in vitro and in vivo experiments demonstrated that Lin reduces lipid accumulation, which is mediated through the enhancement of autophagy and the inhibition of the release of inflammatory factors. 16S rRNA analysis revealed that Lin alleviates gut dysbiosis by reducing Firmicutes and Bacteroidetes phyla while increasing the abundance of Akkermansia and Bifidobacterium genera. Mechanistically, Lin activates autophagy via the PI3K/Akt/mTOR pathway, thereby alleviating lipid accumulation and inflammation. These findings suggest that Lin can mitigate NAFLD by inhibiting the activation of the PI3K/Akt/mTOR pathway, highlighting its potential as a promising therapeutic approach for NAFLD.
期刊介绍:
BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.