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

Author(s):Show less -

Sato, Fabio Takeo ^[1] ; Yap, Yu Anne ^[2] ; Crisma, Amanda Rabello ^[3] ; Portovedo, Mariana ^[1] ; Murata, Gilson Masahiro ^[4] ; Hirabara, Sandro Massao ^[5] ; Ribeiro, Willian Rodrigues ^[6] ; Ferreira, Caroline Marcantonio ^[6] ; Cruz, Maysa Mariana ^[7] ; Bertaglia Pereira, Joice Naiara ^[5] ; Payolla, Tanyara Baliani ^[4] ; Sato Guima, Suzana Eiko ^[8] ; Thomas, Andrew Maltez ^[8] ; Setubal, Joao Carlos ^[8] ; Cardoso Alonso-Vale, Maria Isabel ^[7] ; Santos, Marinilce Fagundes ^[9] ; Curi, Rui ^{[4, 10, 5]} ; Marino, Eliana ^[2] ; Vinolo, Marco A. R. ^{[1, 11, 12]}

Affiliation:Show less -

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, BR-13083007 Campinas - Brazil

^[2] Monash Univ, Biomed Discovery Inst, Dept Biochem, Melbourne, Vic 3800 - Australia

^[3] Univ Fed Parana, Dept Clin Anal, BR-80060000 Curitiba, Parana - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil

^[5] Cruzeiro do Sul Univ, Interdisciplinary Postgrad Program Hlth Sci, BR-01506000 Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, BR-09972270 Diadema - Brazil

^[7] Univ Fed Sao Paulo, Dept Biol Sci, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Diadema - Brazil

^[8] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo - Brazil

^[9] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil

^[10] Butantan Inst, BR-05503900 Sao Paulo - Brazil

^[11] Univ Estadual Campinas, Expt Med Res Cluster EMRC, UNICAMP, BR-13083007 Campinas - Brazil

^[12] Univ Estadual Campinas, Obes & Comorbid Res Ctr OCRC, UNICAMP, BR-13083864 Campinas - Brazil

• Document type: Journal article
• Source: CELLS; v. 9, n. 9 SEP 2020.
• Web of Science Citations: 0

Abstract

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-1 beta 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. (AU)

• FAPESP's process: 12/15774-9 - Application of histone deacetylase inhibitors in the treatment of obesity and associated insulin resistance
• Grantee: Fabio Takeo Sato
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/10653-9 - Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro
• Grantee: Marco Aurélio Ramirez Vinolo
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation
• Grantee: Marco Aurélio Ramirez Vinolo
• Support type: Research Grants - Young Investigators Grants - Phase 2