Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
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
Affiliations
Fabio Takeo Sato
Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083007, Brazil
Yu Anne Yap
Department of Biochemistry, Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia
Amanda Rabello Crisma
Department of Clinical Analyses, Federal University of Paraná, Curitiba 80060000, Brazil
Mariana Portovedo
Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083007, Brazil
Gilson Masahiro Murata
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, Brazil
Sandro Massao Hirabara
Interdisciplinary Postgraduate Program in Health Science, Cruzeiro do Sul University, São Paulo 01506000, Brazil
Willian Rodrigues Ribeiro
Department of Pharmaceutics Sciences, Institute of Environmental Chemistry and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, Brazil
Caroline Marcantonio Ferreira
Department of Pharmaceutics Sciences, Institute of Environmental Chemistry and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, Brazil
Maysa Mariana Cruz
Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, Brazil
Joice Naiara Bertaglia Pereira
Interdisciplinary Postgraduate Program in Health Science, Cruzeiro do Sul University, São Paulo 01506000, Brazil
Tanyara Baliani Payolla
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, Brazil
Suzana Eiko Sato Guima
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508000, Brazil
Andrew Maltez Thomas
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508000, Brazil
João Carlos Setubal
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508000, Brazil
Maria Isabel Cardoso Alonso-Vale
Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema 09972270, Brazil
Marinilce Fagundes Santos
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, Brazil
Rui Curi
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, Brazil
Eliana Marino
Department of Biochemistry, Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia
Marco A. R. Vinolo
Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083007, Brazil
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 Il-1β and Tnf-a and increased Il-10, 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.
