Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation
Orlistat reduces obesity by inhibiting gastrointestinal lipases, thereby blocking the absorption and accumulation of triglycerides in the intestine. It has been shown to improve lipid metabolism and alter intestinal microbial communities in animals and humans. However, the impact of Orlistat-induced...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1480500/full |
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| author | Chengyan Huang Yuanhui He Ping Chai Zongxin Liu Sirui Su Yanhui Zhang Yuelan Luo Shuiping Fu |
| author_facet | Chengyan Huang Yuanhui He Ping Chai Zongxin Liu Sirui Su Yanhui Zhang Yuelan Luo Shuiping Fu |
| author_sort | Chengyan Huang |
| collection | DOAJ |
| description | Orlistat reduces obesity by inhibiting gastrointestinal lipases, thereby blocking the absorption and accumulation of triglycerides in the intestine. It has been shown to improve lipid metabolism and alter intestinal microbial communities in animals and humans. However, the impact of Orlistat-induced changes in gut microbiota on obesity requires further investigation. In this study, we found that Orlistat significantly improved metabolic disorders, inhibited fat accumulation, and reshaped the structure of intestinal microbiota. Specifically, it reduced α diversity and increased the relative abundance of Verrucomicrobia and Akkermansia. Notably, antibiotic-induced gut microbiota depletion significantly weakened Orlistat’s effect on improving metabolic disorders. Furthermore, microbiota transplanted from Orlistat-treated mice effectively alleviated lipid metabolic disorders caused by a high-fat diet. We also observed that Orlistat increased food intake in mice and inhibited the synthesis of appetite-regulating hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon (Gcg). However, antibiotic-depleted microbiota mitigated this inhibitory effect. Interestingly, although Orlistat altered the gut microbiota of mice, transplanting these microbiota did not inhibit the synthesis of appetite-regulating hormones. In summary, our results suggest that Orlistat can reshape the gut microbiota, and the altered gut microbiota works synergistically with Orlistat to improve metabolic disorders. This improvement is related to the increased abundance of Verrucomicrobia and Akkermansia. |
| format | Article |
| id | doaj-art-3a40e6fbae7c41d0a07797bb7df847c6 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-3a40e6fbae7c41d0a07797bb7df847c62025-02-06T07:09:56ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-02-011610.3389/fmicb.2025.14805001480500Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulationChengyan Huang0Yuanhui He1Ping Chai2Zongxin Liu3Sirui Su4Yanhui Zhang5Yuelan Luo6Shuiping Fu7Department of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, ChinaDepartment of Obstetrics and Gynecology, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, ChinaDepartment of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, ChinaDepartment of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, ChinaDepartment of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, ChinaDepartment of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, ChinaDepartment of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, ChinaDepartment of Nursing, Fenyang College, Shanxi Medical University, Fengyang, ChinaOrlistat reduces obesity by inhibiting gastrointestinal lipases, thereby blocking the absorption and accumulation of triglycerides in the intestine. It has been shown to improve lipid metabolism and alter intestinal microbial communities in animals and humans. However, the impact of Orlistat-induced changes in gut microbiota on obesity requires further investigation. In this study, we found that Orlistat significantly improved metabolic disorders, inhibited fat accumulation, and reshaped the structure of intestinal microbiota. Specifically, it reduced α diversity and increased the relative abundance of Verrucomicrobia and Akkermansia. Notably, antibiotic-induced gut microbiota depletion significantly weakened Orlistat’s effect on improving metabolic disorders. Furthermore, microbiota transplanted from Orlistat-treated mice effectively alleviated lipid metabolic disorders caused by a high-fat diet. We also observed that Orlistat increased food intake in mice and inhibited the synthesis of appetite-regulating hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon (Gcg). However, antibiotic-depleted microbiota mitigated this inhibitory effect. Interestingly, although Orlistat altered the gut microbiota of mice, transplanting these microbiota did not inhibit the synthesis of appetite-regulating hormones. In summary, our results suggest that Orlistat can reshape the gut microbiota, and the altered gut microbiota works synergistically with Orlistat to improve metabolic disorders. This improvement is related to the increased abundance of Verrucomicrobia and Akkermansia.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1480500/fullOrlistatobesitylipid metabolismgut microbiotamicrobiota transplantation |
| spellingShingle | Chengyan Huang Yuanhui He Ping Chai Zongxin Liu Sirui Su Yanhui Zhang Yuelan Luo Shuiping Fu Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation Frontiers in Microbiology Orlistat obesity lipid metabolism gut microbiota microbiota transplantation |
| title | Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation |
| title_full | Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation |
| title_fullStr | Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation |
| title_full_unstemmed | Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation |
| title_short | Orlistat ameliorates lipid dysmetabolism in high-fat diet-induced mice via gut microbiota modulation |
| title_sort | orlistat ameliorates lipid dysmetabolism in high fat diet induced mice via gut microbiota modulation |
| topic | Orlistat obesity lipid metabolism gut microbiota microbiota transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1480500/full |
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