Microbiota determines insulin sensitivity in TLR2-KO mice
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.lfs.2019.116793 http://hdl.handle.net/11449/188029 |
Resumo: | Introduction: Environmental factors have a key role in the control of gut microbiota and obesity. TLR2 knockout (TLR2−/−) mice in some housing conditions are protected from diet-induced insulin resistance. However, in our housing conditions these animals are not protected from diet-induced insulin-resistance. Aim: The aim of the present study was to investigate the influence of our animal housing conditions on the gut microbiota, glucose tolerance and insulin sensitivity in TLR2−/− mice. Material and methods: The microbiota was investigated by metagenomics, associated with hyperinsulinemic euglycemic clamp and GTT associated with insulin signaling through immunoblotting. Results: The results showed that TLR2−/− mice in our housing conditions presented a phenotype of metabolic syndrome characterized by insulin resistance, glucose intolerance and increase in body weight. This phenotype was associated with differences in microbiota in TLR2−/− mice that showed a decrease in the Proteobacteria and Bacteroidetes phyla and an increase in the Firmicutesphylum, associated with and in increase in the Oscillospira and Ruminococcus genera. Furthermore there is also an increase in circulating LPS and subclinical inflammation in TLR2−/−. The molecular mechanism that account for insulin resistance was an activation of TLR4, associated with ER stress and JNK activation. The phenotype and metabolic behavior was reversed by antibiotic treatment and reproduced in WT mice by microbiota transplantation. Conclusions: Our data show, for the first time, that the intestinal microbiota can induce insulin resistance and obesity in an animal model that is genetically protected from these processes. |
id |
UNSP_585cae13942999715c81fe29aaa94074 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/188029 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Microbiota determines insulin sensitivity in TLR2-KO miceGenetic protectionGut microbiotaInsulin resistanceLPSTLR2Introduction: Environmental factors have a key role in the control of gut microbiota and obesity. TLR2 knockout (TLR2−/−) mice in some housing conditions are protected from diet-induced insulin resistance. However, in our housing conditions these animals are not protected from diet-induced insulin-resistance. Aim: The aim of the present study was to investigate the influence of our animal housing conditions on the gut microbiota, glucose tolerance and insulin sensitivity in TLR2−/− mice. Material and methods: The microbiota was investigated by metagenomics, associated with hyperinsulinemic euglycemic clamp and GTT associated with insulin signaling through immunoblotting. Results: The results showed that TLR2−/− mice in our housing conditions presented a phenotype of metabolic syndrome characterized by insulin resistance, glucose intolerance and increase in body weight. This phenotype was associated with differences in microbiota in TLR2−/− mice that showed a decrease in the Proteobacteria and Bacteroidetes phyla and an increase in the Firmicutesphylum, associated with and in increase in the Oscillospira and Ruminococcus genera. Furthermore there is also an increase in circulating LPS and subclinical inflammation in TLR2−/−. The molecular mechanism that account for insulin resistance was an activation of TLR4, associated with ER stress and JNK activation. The phenotype and metabolic behavior was reversed by antibiotic treatment and reproduced in WT mice by microbiota transplantation. Conclusions: Our data show, for the first time, that the intestinal microbiota can induce insulin resistance and obesity in an animal model that is genetically protected from these processes.Instituto Nacional de Ciência e Tecnologia de Obesidade e DiabetesDepartment of Internal Medicine-FCM University of Campinas-UNICAMPInterdisciplinary Post-Graduate Program in Health Science Cruzeiro do Sul UniversityDepartment of Physical Education Biosciences Institute São Paulo State University (UNESP)Graduate Program in Nutritional and Sport Sciences and Metabolism School of Applied Sciences University of Campinas- UNICAMPDepartment of Physical Education Biosciences Institute São Paulo State University (UNESP)Instituto Nacional de Ciência e Tecnologia de Obesidade e Diabetes: 465693/2014-8Universidade Estadual de Campinas (UNICAMP)Cruzeiro do Sul UniversityUniversidade Estadual Paulista (Unesp)Guadagnini, DiozeRocha, Guilherme ZweigSantos, AndreyAssalin, Heloisa BalanHirabara, Sandro MassaoCuri, RuiOliveira, Alexandre Gabarra [UNESP]Prada, Patricia O.Saad, Mario J.A.2019-10-06T15:54:59Z2019-10-06T15:54:59Z2019-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.lfs.2019.116793Life Sciences, v. 234.1879-06310024-3205http://hdl.handle.net/11449/18802910.1016/j.lfs.2019.1167932-s2.0-85071483408Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLife Sciencesinfo:eu-repo/semantics/openAccess2021-10-23T01:58:01Zoai:repositorio.unesp.br:11449/188029Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:04:33.029697Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Microbiota determines insulin sensitivity in TLR2-KO mice |
title |
Microbiota determines insulin sensitivity in TLR2-KO mice |
spellingShingle |
Microbiota determines insulin sensitivity in TLR2-KO mice Guadagnini, Dioze Genetic protection Gut microbiota Insulin resistance LPS TLR2 |
title_short |
Microbiota determines insulin sensitivity in TLR2-KO mice |
title_full |
Microbiota determines insulin sensitivity in TLR2-KO mice |
title_fullStr |
Microbiota determines insulin sensitivity in TLR2-KO mice |
title_full_unstemmed |
Microbiota determines insulin sensitivity in TLR2-KO mice |
title_sort |
Microbiota determines insulin sensitivity in TLR2-KO mice |
author |
Guadagnini, Dioze |
author_facet |
Guadagnini, Dioze Rocha, Guilherme Zweig Santos, Andrey Assalin, Heloisa Balan Hirabara, Sandro Massao Curi, Rui Oliveira, Alexandre Gabarra [UNESP] Prada, Patricia O. Saad, Mario J.A. |
author_role |
author |
author2 |
Rocha, Guilherme Zweig Santos, Andrey Assalin, Heloisa Balan Hirabara, Sandro Massao Curi, Rui Oliveira, Alexandre Gabarra [UNESP] Prada, Patricia O. Saad, Mario J.A. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Cruzeiro do Sul University Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Guadagnini, Dioze Rocha, Guilherme Zweig Santos, Andrey Assalin, Heloisa Balan Hirabara, Sandro Massao Curi, Rui Oliveira, Alexandre Gabarra [UNESP] Prada, Patricia O. Saad, Mario J.A. |
dc.subject.por.fl_str_mv |
Genetic protection Gut microbiota Insulin resistance LPS TLR2 |
topic |
Genetic protection Gut microbiota Insulin resistance LPS TLR2 |
description |
Introduction: Environmental factors have a key role in the control of gut microbiota and obesity. TLR2 knockout (TLR2−/−) mice in some housing conditions are protected from diet-induced insulin resistance. However, in our housing conditions these animals are not protected from diet-induced insulin-resistance. Aim: The aim of the present study was to investigate the influence of our animal housing conditions on the gut microbiota, glucose tolerance and insulin sensitivity in TLR2−/− mice. Material and methods: The microbiota was investigated by metagenomics, associated with hyperinsulinemic euglycemic clamp and GTT associated with insulin signaling through immunoblotting. Results: The results showed that TLR2−/− mice in our housing conditions presented a phenotype of metabolic syndrome characterized by insulin resistance, glucose intolerance and increase in body weight. This phenotype was associated with differences in microbiota in TLR2−/− mice that showed a decrease in the Proteobacteria and Bacteroidetes phyla and an increase in the Firmicutesphylum, associated with and in increase in the Oscillospira and Ruminococcus genera. Furthermore there is also an increase in circulating LPS and subclinical inflammation in TLR2−/−. The molecular mechanism that account for insulin resistance was an activation of TLR4, associated with ER stress and JNK activation. The phenotype and metabolic behavior was reversed by antibiotic treatment and reproduced in WT mice by microbiota transplantation. Conclusions: Our data show, for the first time, that the intestinal microbiota can induce insulin resistance and obesity in an animal model that is genetically protected from these processes. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T15:54:59Z 2019-10-06T15:54:59Z 2019-10-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.lfs.2019.116793 Life Sciences, v. 234. 1879-0631 0024-3205 http://hdl.handle.net/11449/188029 10.1016/j.lfs.2019.116793 2-s2.0-85071483408 |
url |
http://dx.doi.org/10.1016/j.lfs.2019.116793 http://hdl.handle.net/11449/188029 |
identifier_str_mv |
Life Sciences, v. 234. 1879-0631 0024-3205 10.1016/j.lfs.2019.116793 2-s2.0-85071483408 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Life Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128889993560064 |