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Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota
This study aimed to evaluate the possible anti-obesity effects of orlistat and ezetimibe and determine the mechanism by which they alter the composition of gut microbiota and short-chain fatty acids (SCFAs) in mice with a high-fat diet (HFD)-induced obesity. Eighty male, specific pathogen-free C57BL...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9421266/ https://www.ncbi.nlm.nih.gov/pubmed/36046024 http://dx.doi.org/10.3389/fmicb.2022.908327 |
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author | Jin, Jin Wang, Jiani Cheng, Ruyue Ren, Yan Miao, Zhonghua Luo, Yating Zhou, Qingqing Xue, Yigui Shen, Xi He, Fang Tian, Haoming |
author_facet | Jin, Jin Wang, Jiani Cheng, Ruyue Ren, Yan Miao, Zhonghua Luo, Yating Zhou, Qingqing Xue, Yigui Shen, Xi He, Fang Tian, Haoming |
author_sort | Jin, Jin |
collection | PubMed |
description | This study aimed to evaluate the possible anti-obesity effects of orlistat and ezetimibe and determine the mechanism by which they alter the composition of gut microbiota and short-chain fatty acids (SCFAs) in mice with a high-fat diet (HFD)-induced obesity. Eighty male, specific pathogen-free C57BL/6J mice aged 3 weeks were divided into four groups (n = 20). The NCD group was fed with a normal diet, and the HFD, HFD+ORL, and HFD+EZE groups were fed with HFD for 20 weeks. From the 13th week onward, the HFD+ORL and HFD+EZE groups were administered with orlistat and ezetimibe, respectively. The glucose and lipid metabolism of the tested mice were evaluated by analyzing blood biochemical indicators during the intervention. Furthermore, the changes in the structure of the fecal microbiota and the fecal SCFA content were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry, respectively. HFD induced the obesity phenotype in mice. Compared to the HFD group, the body weight, visceral fat-to-body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and oral glucose tolerance test (OGTT) of the HFD+ORL group significantly decreased, whereas fecal butyric acid levels significantly increased. Ezetimibe intervention significantly reduced the OGTT, serum TC, and HDL-C levels only. The α-diversity of the gut microbiota significantly decreased after intervention with orlistat and ezetimibe. Orlistat altered the relative abundance of some bacteria in the fecal microbiota. The populations of Firmicutes, Alistipes, and Desulfovibrio decreased, whereas those of Verrucomicrobia and Akkermansia significantly increased. Ezetimibe caused changes only in some low-abundance bacteria, as manifested by a decrease in Proteobacteria and Desulfovibrio, and an increase in Bacteroides. The administration of orlistat and ezetimibe can characteristically influence the body weight and serum lipid metabolism, and glucolipid levels in diet-induced obese mice and is accompanied by significant changes in the gut microbiota and SCFAs. These results suggest that the two drugs might exert their own specific anti-obesity effects by modulating the gut microbiota in a different manner. The enhanced health-promoting effect of orlistat might result from its stronger ability to alter the gut microbiota and SCFAs, at least partly. |
format | Online Article Text |
id | pubmed-9421266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94212662022-08-30 Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota Jin, Jin Wang, Jiani Cheng, Ruyue Ren, Yan Miao, Zhonghua Luo, Yating Zhou, Qingqing Xue, Yigui Shen, Xi He, Fang Tian, Haoming Front Microbiol Microbiology This study aimed to evaluate the possible anti-obesity effects of orlistat and ezetimibe and determine the mechanism by which they alter the composition of gut microbiota and short-chain fatty acids (SCFAs) in mice with a high-fat diet (HFD)-induced obesity. Eighty male, specific pathogen-free C57BL/6J mice aged 3 weeks were divided into four groups (n = 20). The NCD group was fed with a normal diet, and the HFD, HFD+ORL, and HFD+EZE groups were fed with HFD for 20 weeks. From the 13th week onward, the HFD+ORL and HFD+EZE groups were administered with orlistat and ezetimibe, respectively. The glucose and lipid metabolism of the tested mice were evaluated by analyzing blood biochemical indicators during the intervention. Furthermore, the changes in the structure of the fecal microbiota and the fecal SCFA content were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry, respectively. HFD induced the obesity phenotype in mice. Compared to the HFD group, the body weight, visceral fat-to-body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and oral glucose tolerance test (OGTT) of the HFD+ORL group significantly decreased, whereas fecal butyric acid levels significantly increased. Ezetimibe intervention significantly reduced the OGTT, serum TC, and HDL-C levels only. The α-diversity of the gut microbiota significantly decreased after intervention with orlistat and ezetimibe. Orlistat altered the relative abundance of some bacteria in the fecal microbiota. The populations of Firmicutes, Alistipes, and Desulfovibrio decreased, whereas those of Verrucomicrobia and Akkermansia significantly increased. Ezetimibe caused changes only in some low-abundance bacteria, as manifested by a decrease in Proteobacteria and Desulfovibrio, and an increase in Bacteroides. The administration of orlistat and ezetimibe can characteristically influence the body weight and serum lipid metabolism, and glucolipid levels in diet-induced obese mice and is accompanied by significant changes in the gut microbiota and SCFAs. These results suggest that the two drugs might exert their own specific anti-obesity effects by modulating the gut microbiota in a different manner. The enhanced health-promoting effect of orlistat might result from its stronger ability to alter the gut microbiota and SCFAs, at least partly. Frontiers Media S.A. 2022-08-15 /pmc/articles/PMC9421266/ /pubmed/36046024 http://dx.doi.org/10.3389/fmicb.2022.908327 Text en Copyright © 2022 Jin, Wang, Cheng, Ren, Miao, Luo, Zhou, Xue, Shen, He and Tian. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Jin, Jin Wang, Jiani Cheng, Ruyue Ren, Yan Miao, Zhonghua Luo, Yating Zhou, Qingqing Xue, Yigui Shen, Xi He, Fang Tian, Haoming Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
title | Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
title_full | Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
title_fullStr | Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
title_full_unstemmed | Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
title_short | Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
title_sort | orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9421266/ https://www.ncbi.nlm.nih.gov/pubmed/36046024 http://dx.doi.org/10.3389/fmicb.2022.908327 |
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