Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism
Abstract Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively al...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | npj Science of Food |
| Online Access: | https://doi.org/10.1038/s41538-022-00156-0 |
| _version_ | 1828742892671205376 |
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| author | Yaxin Zhang Yuyan Gu Jing Jiang Xiaobing Cui Saibo Cheng Linling Liu Zhiyong Huang Rongxin Liao Peng Zhao Jieying Yu Jing Wang Yuhua Jia Wen Jin Fenghua Zhou |
| author_facet | Yaxin Zhang Yuyan Gu Jing Jiang Xiaobing Cui Saibo Cheng Linling Liu Zhiyong Huang Rongxin Liao Peng Zhao Jieying Yu Jing Wang Yuhua Jia Wen Jin Fenghua Zhou |
| author_sort | Yaxin Zhang |
| collection | DOAJ |
| description | Abstract Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia. |
| first_indexed | 2024-04-13T01:27:58Z |
| format | Article |
| id | doaj.art-b88895b306304c2ab63d8614d639b376 |
| institution | Directory Open Access Journal |
| issn | 2396-8370 |
| language | English |
| last_indexed | 2024-04-13T01:27:58Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Science of Food |
| spelling | doaj.art-b88895b306304c2ab63d8614d639b3762022-12-22T03:08:35ZengNature Portfolionpj Science of Food2396-83702022-08-016111410.1038/s41538-022-00156-0Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolismYaxin Zhang0Yuyan Gu1Jing Jiang2Xiaobing Cui3Saibo Cheng4Linling Liu5Zhiyong Huang6Rongxin Liao7Peng Zhao8Jieying Yu9Jing Wang10Yuhua Jia11Wen Jin12Fenghua Zhou13Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversityDepartment of Cardiology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversityDepartment of Otolaryngology, The Third Affiliated Hospital of Southern Medical UniversityCenter of TCM Preventive Treatment, Integrated Hospital of Traditional Chinese Medicine, Southern Medical UniversityCenter of TCM Preventive Treatment, Integrated Hospital of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversityDepartment of Cardiac Intensive Care Unit, Cardiovascular Hospital, Guangdong Second Provincial General HospitalIntegrated Hospital of Traditional Chinese Medicine, Southern Medical UniversityAbstract Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia.https://doi.org/10.1038/s41538-022-00156-0 |
| spellingShingle | Yaxin Zhang Yuyan Gu Jing Jiang Xiaobing Cui Saibo Cheng Linling Liu Zhiyong Huang Rongxin Liao Peng Zhao Jieying Yu Jing Wang Yuhua Jia Wen Jin Fenghua Zhou Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism npj Science of Food |
| title | Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism |
| title_full | Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism |
| title_fullStr | Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism |
| title_full_unstemmed | Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism |
| title_short | Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism |
| title_sort | stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism |
| url | https://doi.org/10.1038/s41538-022-00156-0 |
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