Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice

• Published in: International journal of molecular sciences Vol. 25; no. 10; p. 5274
• Main Authors: Yang, Ching-Wei, Liu, Hsuan-Miao, Chang, Zi-Yu, Liu, Geng-Hao, Chang, Hen-Hong, Huang, Po-Yu, Lee, Tzung-Yan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.05.2024
• Subjects: Akkermansia; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11 - genetics; ATP Binding Cassette Transporter, Subfamily B, Member 11 - metabolism; B cells; Bile; Cancer; Cholesterol 7-alpha-Hydroxylase - genetics; Cholesterol 7-alpha-Hydroxylase - metabolism; Cytokines; Cytotoxicity; Diabetes; Diet, High-Fat - adverse effects; Dysbiosis; farnesoid X receptor; Fatty acids; Gastrointestinal Microbiome - drug effects; gut microbiota; Health aspects; Hepatocytes - drug effects; Hepatocytes - metabolism; Isoflavones - pharmacology; Lipid Metabolism - drug effects; Lipid peroxidation; Lipids; Liver; Liver - drug effects; Liver - metabolism; Liver diseases; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Microbiota; Microbiota (Symbiotic organisms); mitochondrial function; mitophagy; obese; Obesity; Obesity - drug therapy; Obesity - metabolism; Organic Anion Transporters, Sodium-Dependent - genetics; Organic Anion Transporters, Sodium-Dependent - metabolism; Oxidative stress; Proteins; puerarin; Receptors, Cytoplasmic and Nuclear - metabolism; Risk factors; Symporters - genetics; Symporters - metabolism; Transcription factors; Tumor necrosis factor-TNF; Type 2 diabetes; United Kingdom; Taiwan; mitochondrial function; mitophagy; puerarin; farnesoid X receptor; gut microbiota; obese
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25105274

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin's beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the / ratio, and the abundance of and . This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin's potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.