Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. M...

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Main Authors: Fabio Takeo Sato, Yu Anne Yap, Amanda Rabello Crisma, Mariana Portovedo, Gilson Masahiro Murata, Sandro Massao Hirabara, Willian Rodrigues Ribeiro, Caroline Marcantonio Ferreira, Maysa Mariana Cruz, Joice Naiara Bertaglia Pereira, Tanyara Baliani Payolla, Suzana Eiko Sato Guima, Andrew Maltez Thomas, João Carlos Setubal, Maria Isabel Cardoso Alonso-Vale, Marinilce Fagundes Santos, Rui Curi, Eliana Marino, Marco A. R. Vinolo
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/9/9/2007
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author Fabio Takeo Sato
Yu Anne Yap
Amanda Rabello Crisma
Mariana Portovedo
Gilson Masahiro Murata
Sandro Massao Hirabara
Willian Rodrigues Ribeiro
Caroline Marcantonio Ferreira
Maysa Mariana Cruz
Joice Naiara Bertaglia Pereira
Tanyara Baliani Payolla
Suzana Eiko Sato Guima
Andrew Maltez Thomas
João Carlos Setubal
Maria Isabel Cardoso Alonso-Vale
Marinilce Fagundes Santos
Rui Curi
Eliana Marino
Marco A. R. Vinolo
author_facet Fabio Takeo Sato
Yu Anne Yap
Amanda Rabello Crisma
Mariana Portovedo
Gilson Masahiro Murata
Sandro Massao Hirabara
Willian Rodrigues Ribeiro
Caroline Marcantonio Ferreira
Maysa Mariana Cruz
Joice Naiara Bertaglia Pereira
Tanyara Baliani Payolla
Suzana Eiko Sato Guima
Andrew Maltez Thomas
João Carlos Setubal
Maria Isabel Cardoso Alonso-Vale
Marinilce Fagundes Santos
Rui Curi
Eliana Marino
Marco A. R. Vinolo
author_sort Fabio Takeo Sato
collection DOAJ
description Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of <i>Il-1β</i> and <i>Tnf-a</i> and increased <i>Il-10</i>, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.
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spelling doaj.art-951345acd32f4b8292d95047e44f900b2023-11-20T12:07:31ZengMDPI AGCells2073-44092020-09-0199200710.3390/cells9092007Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent MechanismFabio Takeo Sato0Yu Anne Yap1Amanda Rabello Crisma2Mariana Portovedo3Gilson Masahiro Murata4Sandro Massao Hirabara5Willian Rodrigues Ribeiro6Caroline Marcantonio Ferreira7Maysa Mariana Cruz8Joice Naiara Bertaglia Pereira9Tanyara Baliani Payolla10Suzana Eiko Sato Guima11Andrew Maltez Thomas12João Carlos Setubal13Maria Isabel Cardoso Alonso-Vale14Marinilce Fagundes Santos15Rui Curi16Eliana Marino17Marco A. R. Vinolo18Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083007, BrazilDepartment of Biochemistry, Biomedicine Discovery Institute, Monash University, Melbourne 3800, AustraliaDepartment of Clinical Analyses, Federal University of Paraná, Curitiba 80060000, BrazilDepartment of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083007, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, BrazilInterdisciplinary Postgraduate Program in Health Science, Cruzeiro do Sul University, São Paulo 01506000, BrazilDepartment of Pharmaceutics Sciences, Institute of Environmental Chemistry and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, BrazilDepartment of Pharmaceutics Sciences, Institute of Environmental Chemistry and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, BrazilDepartment of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, BrazilInterdisciplinary Postgraduate Program in Health Science, Cruzeiro do Sul University, São Paulo 01506000, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, BrazilDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508000, BrazilDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508000, BrazilDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508000, BrazilDepartment of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, BrazilDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, BrazilDepartment of Biochemistry, Biomedicine Discovery Institute, Monash University, Melbourne 3800, AustraliaDepartment of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083007, BrazilObesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of <i>Il-1β</i> and <i>Tnf-a</i> and increased <i>Il-10</i>, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.https://www.mdpi.com/2073-4409/9/9/2007butyratemicrobiotainsulin resistancedysbiosis
spellingShingle Fabio Takeo Sato
Yu Anne Yap
Amanda Rabello Crisma
Mariana Portovedo
Gilson Masahiro Murata
Sandro Massao Hirabara
Willian Rodrigues Ribeiro
Caroline Marcantonio Ferreira
Maysa Mariana Cruz
Joice Naiara Bertaglia Pereira
Tanyara Baliani Payolla
Suzana Eiko Sato Guima
Andrew Maltez Thomas
João Carlos Setubal
Maria Isabel Cardoso Alonso-Vale
Marinilce Fagundes Santos
Rui Curi
Eliana Marino
Marco A. R. Vinolo
Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
Cells
butyrate
microbiota
insulin resistance
dysbiosis
title Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
title_full Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
title_fullStr Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
title_full_unstemmed Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
title_short Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
title_sort tributyrin attenuates metabolic and inflammatory changes associated with obesity through a gpr109a dependent mechanism
topic butyrate
microbiota
insulin resistance
dysbiosis
url https://www.mdpi.com/2073-4409/9/9/2007
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