Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice
Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise und...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2390136 |
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| author | Xiaoqiang Zhu Xiaojuan Dai Lijun Zhao Jing Li Yanhong Zhu Wenjuan He Xinlei Guan Tao Wu Li Liu Hongping Song Liang Lei |
| author_facet | Xiaoqiang Zhu Xiaojuan Dai Lijun Zhao Jing Li Yanhong Zhu Wenjuan He Xinlei Guan Tao Wu Li Liu Hongping Song Liang Lei |
| author_sort | Xiaoqiang Zhu |
| collection | DOAJ |
| description | Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases. |
| format | Article |
| id | doaj-art-6710bc2ae19b45fc952271d3183eba4e |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-6710bc2ae19b45fc952271d3183eba4e2025-08-20T03:12:51ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2390136Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in miceXiaoqiang Zhu0Xiaojuan Dai1Lijun Zhao2Jing Li3Yanhong Zhu4Wenjuan He5Xinlei Guan6Tao Wu7Li Liu8Hongping Song9Liang Lei10Central Laboratory, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Gastroenterology, Wuhan Fourth Hospital, Wuhan, ChinaNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, ChinaPharmaceutical Department, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, ChinaCentral Laboratory, Wuhan Fourth Hospital, Wuhan, ChinaCentral Laboratory, Wuhan Fourth Hospital, Wuhan, ChinaCentral Laboratory, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Pharmacy, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Pharmacy, Wuhan Fourth Hospital, Wuhan, ChinaCentral Laboratory, Wuhan Fourth Hospital, Wuhan, ChinaAbdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.https://www.tandfonline.com/doi/10.1080/19490976.2024.2390136Quercetinmetabolic syndromeenergy metabolismgut microbiotabile acids |
| spellingShingle | Xiaoqiang Zhu Xiaojuan Dai Lijun Zhao Jing Li Yanhong Zhu Wenjuan He Xinlei Guan Tao Wu Li Liu Hongping Song Liang Lei Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice Gut Microbes Quercetin metabolic syndrome energy metabolism gut microbiota bile acids |
| title | Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice |
| title_full | Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice |
| title_fullStr | Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice |
| title_full_unstemmed | Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice |
| title_short | Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice |
| title_sort | quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota bile acids crosstalk in mice |
| topic | Quercetin metabolic syndrome energy metabolism gut microbiota bile acids |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2390136 |
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