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Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice

BACKGROUND: Although gut hormone glucagon-like peptide 1 (GLP-1) has been widely used for treating diabetes, the extremely short half-life greatly limits its application. The purpose of this study is to explore the effects of an engineered bacteria with expression of GLP-1 on obese mice induced by h...

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Autores principales: Wang, Lingfang, Chen, Tingtao, Wang, Huan, Wu, Xiaoli, Cao, Qing, Wen, Ke, Deng, Ke-Yu, Xin, Hongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959774/
https://www.ncbi.nlm.nih.gov/pubmed/33732656
http://dx.doi.org/10.3389/fcimb.2021.595575
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author Wang, Lingfang
Chen, Tingtao
Wang, Huan
Wu, Xiaoli
Cao, Qing
Wen, Ke
Deng, Ke-Yu
Xin, Hongbo
author_facet Wang, Lingfang
Chen, Tingtao
Wang, Huan
Wu, Xiaoli
Cao, Qing
Wen, Ke
Deng, Ke-Yu
Xin, Hongbo
author_sort Wang, Lingfang
collection PubMed
description BACKGROUND: Although gut hormone glucagon-like peptide 1 (GLP-1) has been widely used for treating diabetes, the extremely short half-life greatly limits its application. The purpose of this study is to explore the effects of an engineered bacteria with expression of GLP-1 on obese mice induced by high fat diet (HFD). METHODS: The engineered strain of MG1363-pMG36e-GLP-1 (M-GLP-1) was constructed and its anti-obesity effects were evaluated in vivo. The bodyweight, the morphology of adipose and liver tissue, and liver function were examined. Quantitative RT-PCR and Western blot were used to measure the expressions of the genes involved in fatty acid oxidation synthesis. The intestinal microbial diversity was detected with high-throughput sequencing analysis. RESULTS: The engineered bacteria could produce GLP-1. It also significantly decreased the bodyweight and improved the glucose intolerance in the obese mice induced by HFD. Moreover, the strain also reduced the triglyceride (TG) in serum, protected liver, as well as decreased the intracellular TG in liver tissues of the obese mice. Furthermore, our results showed that the expressions of the genes including peroxisome proliferator-activated receptors α (PPARα) and its target genes were enhanced in liver tissues when mice treated with M-GLP-1. Finally, we found that the engineered strain markedly increased intestinal microbial diversity. CONCLUSION: Our results suggested the genetically engineered bacteria that constitutively secreted GLP-1 could improve obesity and the mechanism may be related to promoting fatty acid oxidation and increasing intestinal microbial diversity of the obese mice.
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spelling pubmed-79597742021-03-16 Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice Wang, Lingfang Chen, Tingtao Wang, Huan Wu, Xiaoli Cao, Qing Wen, Ke Deng, Ke-Yu Xin, Hongbo Front Cell Infect Microbiol Cellular and Infection Microbiology BACKGROUND: Although gut hormone glucagon-like peptide 1 (GLP-1) has been widely used for treating diabetes, the extremely short half-life greatly limits its application. The purpose of this study is to explore the effects of an engineered bacteria with expression of GLP-1 on obese mice induced by high fat diet (HFD). METHODS: The engineered strain of MG1363-pMG36e-GLP-1 (M-GLP-1) was constructed and its anti-obesity effects were evaluated in vivo. The bodyweight, the morphology of adipose and liver tissue, and liver function were examined. Quantitative RT-PCR and Western blot were used to measure the expressions of the genes involved in fatty acid oxidation synthesis. The intestinal microbial diversity was detected with high-throughput sequencing analysis. RESULTS: The engineered bacteria could produce GLP-1. It also significantly decreased the bodyweight and improved the glucose intolerance in the obese mice induced by HFD. Moreover, the strain also reduced the triglyceride (TG) in serum, protected liver, as well as decreased the intracellular TG in liver tissues of the obese mice. Furthermore, our results showed that the expressions of the genes including peroxisome proliferator-activated receptors α (PPARα) and its target genes were enhanced in liver tissues when mice treated with M-GLP-1. Finally, we found that the engineered strain markedly increased intestinal microbial diversity. CONCLUSION: Our results suggested the genetically engineered bacteria that constitutively secreted GLP-1 could improve obesity and the mechanism may be related to promoting fatty acid oxidation and increasing intestinal microbial diversity of the obese mice. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7959774/ /pubmed/33732656 http://dx.doi.org/10.3389/fcimb.2021.595575 Text en Copyright © 2021 Wang, Chen, Wang, Wu, Cao, Wen, Deng and Xin http://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, Lingfang
Chen, Tingtao
Wang, Huan
Wu, Xiaoli
Cao, Qing
Wen, Ke
Deng, Ke-Yu
Xin, Hongbo
Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
title Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
title_full Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
title_fullStr Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
title_full_unstemmed Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
title_short Engineered Bacteria of MG1363-pMG36e-GLP-1 Attenuated Obesity-Induced by High Fat Diet in Mice
title_sort engineered bacteria of mg1363-pmg36e-glp-1 attenuated obesity-induced by high fat diet in mice
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959774/
https://www.ncbi.nlm.nih.gov/pubmed/33732656
http://dx.doi.org/10.3389/fcimb.2021.595575
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