Application of tributyrin in the treatment of obesity and insulin resistance associated in experimental model

Author(s)

Fabio Takeo Sato

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2018-05-21

Examining board members

Marco Aurélio Ramirez Vinolo; Amanda Rabello Crisma; Leonardo dos Reis Silveira; Sandro Massao Hirabara

• Advisor: Marco Aurélio Ramirez Vinolo

Abstract

Butyrate is a short chain fatty acid (SCFA) produced by the intestinal microbiota from dietary fiber. Increased production of this metabolite by fiber intake or diet supplementation has been associated with a protective effect against the development of metabolic and inflammatory changes associated with obesity. However, the mechanisms underlying these effects are not defined. Additionally, it is not clear whether increasing butyrate availability has any beneficial effect on obese individuals and it could be used in the treatment of this condition. The present study investigated the effect of tributyrin (Tb), a pro-drug of butyrate, on obese mice and explored the involvement of SCFAs receptors, GPR43 and GPR109a, in its effects. For this, mice were kept on high fat diet (HFD) for 8 weeks and then were treated with Tb (2 g/kg b.w., three times a week) or placebo for another 6 weeks. Obese mice treated with Tb had lower weight gain and a decrease in liver weight and hepatic triglycerides content. A reduction of fasting glucose, improvement of glucose tolerance and reduction in plasmatic concentrations of non-esterified fatty acids (NEFA) were also observed. Although no difference in epididymal white adipose tissue weight was observed, a reduction of M1-macrophages numbers and expression of inflammatory markers (Il-1beta, Mcp-1, F4/80 and Cd11c) was present in Tb mice. Experiments in Gpr43 and Gpr109a-deficient mice (Gpr43-/- and Gpr109a-/- mice) indicate that the improvement in glucose metabolism caused by Tb treatment is dependent of GPR109a activation and the underlying mechanism could involve T regulatory cells. Our results indicate that Tb attenuate, but do not revert, metabolic and inflammatory changes present in obese animals through a GPR109a dependent mechanism (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 Opportunities: Scholarships in Brazil - Doctorate