TY - JOUR
T1 - Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice
AU - Yang, Ching Wei
AU - Liu, Hsuan Miao
AU - Chang, Zi Yu
AU - Liu, Geng Hao
AU - Chang, Hen Hong
AU - Huang, Po Yu
AU - Lee, Tzung Yan
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/5/12
Y1 - 2024/5/12
N2 - 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 Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. 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.
AB - 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 Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. 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.
KW - farnesoid X receptor
KW - gut microbiota
KW - mitochondrial function
KW - mitophagy
KW - obese
KW - puerarin
KW - ATP Binding Cassette Transporter, Subfamily B, Member 11/metabolism
KW - Male
KW - Diet, High-Fat/adverse effects
KW - Obesity/metabolism
KW - Dysbiosis
KW - Liver/metabolism
KW - Gastrointestinal Microbiome/drug effects
KW - Isoflavones/pharmacology
KW - Mice, Inbred C57BL
KW - Lipid Metabolism/drug effects
KW - Symporters/metabolism
KW - Receptors, Cytoplasmic and Nuclear/metabolism
KW - Cholesterol 7-alpha-Hydroxylase/metabolism
KW - Mice, Knockout
KW - Organic Anion Transporters, Sodium-Dependent/metabolism
KW - Animals
KW - Hepatocytes/metabolism
KW - Mice, Obese
KW - Akkermansia
KW - Mice
UR - http://www.scopus.com/inward/record.url?scp=85194218552&partnerID=8YFLogxK
U2 - 10.3390/ijms25105274
DO - 10.3390/ijms25105274
M3 - 文章
C2 - 38791314
SN - 1661-6596
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 10
M1 - 5274
ER -