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Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice

Fenofibrate, as a lipid-lowering drug, has been reported to have a protective effect on the retina independent with plasma lipid levels. This study aimed to investigate that the ameliorative effects of fenofibrate on systemic and retinal inflammation, as well as gut microbiota dysbiosis in high-fat...

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Autores principales: Wang, Xue, Yu, Chaofeng, Liu, Xiaomei, Yang, Jiasong, Feng, Yuliang, Wu, Yajun, Xu, Yali, Zhu, Yihua, Li, Wensheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201033/
https://www.ncbi.nlm.nih.gov/pubmed/35719341
http://dx.doi.org/10.3389/fcimb.2022.839592
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author Wang, Xue
Yu, Chaofeng
Liu, Xiaomei
Yang, Jiasong
Feng, Yuliang
Wu, Yajun
Xu, Yali
Zhu, Yihua
Li, Wensheng
author_facet Wang, Xue
Yu, Chaofeng
Liu, Xiaomei
Yang, Jiasong
Feng, Yuliang
Wu, Yajun
Xu, Yali
Zhu, Yihua
Li, Wensheng
author_sort Wang, Xue
collection PubMed
description Fenofibrate, as a lipid-lowering drug, has been reported to have a protective effect on the retina independent with plasma lipid levels. This study aimed to investigate that the ameliorative effects of fenofibrate on systemic and retinal inflammation, as well as gut microbiota dysbiosis in high-fat diet (HFD)-induced mice. C57BL/6J mice were randomly allocated into four groups: standard diet (SD) group; HFD group; SD plus fenofibrate (SD_ Fe) group; HFD plus fenofibrate (HFD_ Fe) group. After successfully establishing models (5 months), indicators associated with lipid, gut barrier, inflammation and gut microbiota were investigated. Our results showed that supplementing the HFD with fenofibrate decreased body weight gain, alleviated dyslipidemia and reversed the downregulation of short-chain fatty acid (SCFAs) in serum, retina and feces. Fenofibrate ameliorated intestinal barrier function damage in HFD-induced mice. Fenofibrate coadministration inhibited the levels of inflammatory factor and lipopolysaccharide (LPS) in the serum and attenuated inflammatory response in the retina of HFD-induced mice. Systemic LPS was positively correlated with a series of inflammatory factors in serum and retina, respectively. Fenofibrate supplementation down-regulated the abundances of LPS-associated bacteria in HFD mice, including Firmicutes and Proteobacteria at the phylum level, Desulfovibrionaceae at the family level, as well as unclassified_ Desulfovibrionaceae, Acetatifactor, Flavonifractor, Oscillibacter and Anaerotruncus at the genus level. However, fenofibrate treatment up-regulated the abundances of SCFA-associated bacteria in HFD mice, including Bacteroidetes at the phylum level, Porphyromonadaceae at the family level, as well as unclassified_Porphyromonadaceae, Barnesiella, Alloprevotella and Bifidobacterium at the genus level. In conclusion, our results confirmed fenofibrate could attenuate HFD-induced systemic and retinal inflammation, accompanying with restoration of intestinal barrier damage and modulation of gut microbiota/metabolites. This work provided an explanation for the ameliorative effects of fenofibrate on HFD-induced systemic and retinal inflammation might be partially related with the modulation of gut microbiota and its metabolites.
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spelling pubmed-92010332022-06-17 Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice Wang, Xue Yu, Chaofeng Liu, Xiaomei Yang, Jiasong Feng, Yuliang Wu, Yajun Xu, Yali Zhu, Yihua Li, Wensheng Front Cell Infect Microbiol Cellular and Infection Microbiology Fenofibrate, as a lipid-lowering drug, has been reported to have a protective effect on the retina independent with plasma lipid levels. This study aimed to investigate that the ameliorative effects of fenofibrate on systemic and retinal inflammation, as well as gut microbiota dysbiosis in high-fat diet (HFD)-induced mice. C57BL/6J mice were randomly allocated into four groups: standard diet (SD) group; HFD group; SD plus fenofibrate (SD_ Fe) group; HFD plus fenofibrate (HFD_ Fe) group. After successfully establishing models (5 months), indicators associated with lipid, gut barrier, inflammation and gut microbiota were investigated. Our results showed that supplementing the HFD with fenofibrate decreased body weight gain, alleviated dyslipidemia and reversed the downregulation of short-chain fatty acid (SCFAs) in serum, retina and feces. Fenofibrate ameliorated intestinal barrier function damage in HFD-induced mice. Fenofibrate coadministration inhibited the levels of inflammatory factor and lipopolysaccharide (LPS) in the serum and attenuated inflammatory response in the retina of HFD-induced mice. Systemic LPS was positively correlated with a series of inflammatory factors in serum and retina, respectively. Fenofibrate supplementation down-regulated the abundances of LPS-associated bacteria in HFD mice, including Firmicutes and Proteobacteria at the phylum level, Desulfovibrionaceae at the family level, as well as unclassified_ Desulfovibrionaceae, Acetatifactor, Flavonifractor, Oscillibacter and Anaerotruncus at the genus level. However, fenofibrate treatment up-regulated the abundances of SCFA-associated bacteria in HFD mice, including Bacteroidetes at the phylum level, Porphyromonadaceae at the family level, as well as unclassified_Porphyromonadaceae, Barnesiella, Alloprevotella and Bifidobacterium at the genus level. In conclusion, our results confirmed fenofibrate could attenuate HFD-induced systemic and retinal inflammation, accompanying with restoration of intestinal barrier damage and modulation of gut microbiota/metabolites. This work provided an explanation for the ameliorative effects of fenofibrate on HFD-induced systemic and retinal inflammation might be partially related with the modulation of gut microbiota and its metabolites. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201033/ /pubmed/35719341 http://dx.doi.org/10.3389/fcimb.2022.839592 Text en Copyright © 2022 Wang, Yu, Liu, Yang, Feng, Wu, Xu, Zhu and Li 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 Cellular and Infection Microbiology
Wang, Xue
Yu, Chaofeng
Liu, Xiaomei
Yang, Jiasong
Feng, Yuliang
Wu, Yajun
Xu, Yali
Zhu, Yihua
Li, Wensheng
Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice
title Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice
title_full Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice
title_fullStr Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice
title_full_unstemmed Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice
title_short Fenofibrate Ameliorated Systemic and Retinal Inflammation and Modulated Gut Microbiota in High-Fat Diet-Induced Mice
title_sort fenofibrate ameliorated systemic and retinal inflammation and modulated gut microbiota in high-fat diet-induced mice
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201033/
https://www.ncbi.nlm.nih.gov/pubmed/35719341
http://dx.doi.org/10.3389/fcimb.2022.839592
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