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Application of histone deacetylase inhibitors in the treatment of obesity and associated insulin resistance

Grant number: 12/15774-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2013
Effective date (End): November 30, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marco Aurélio Ramirez Vinolo
Grantee:Fabio Takeo Sato
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):15/03962-3 - Role of the receptor GPR109A in the effects of tributyrin in mice fed high-fat diet, BE.EP.DR

Abstract

Obesity is a condition in which there is an excessive accumulation of adipose tissue. In Brazil, around 49% of the population is overweight, and 16% is obese. Obesity is associated with other diseases including diabetes mellitus type 2 (DM2), heart disease, hypertension, dyslipidemia and certain types of cancer, being considered a serious public health problem. Obesity is characterized by a chronic subclinical state of inflammation, which is involved in organ dysfunction. In this project, we aim to investigate the effect of histone deacetylase inhibitor (iHDAC), SAHA, and the prodrug of butyrate (tributyrin), which have significant anti-inflammatory effects, on the development of insulin resistance in a murine model of obesity. For this, C57BL/6 male adults mice will receive treatment with iHDAC for a period of 10 weeks concomitant with high fat diet. At the end of the protocol, insulin response (glucose metabolism and signaling to the hormone), lipid parameters (cholesterol, lipoproteins and free fatty acid concentrations), production of inflammatory mediators by peritoneal macrophages and white adipose tissue and activation of inflammatory pathways and insulin signaling in the liver, skeletal muscle and white adipose tissue will be determined. This protocol will also be applied to Ob/ob mice (leptin deficient), which develop obesity and insulin resistance. This project is important not only for understanding the mechanisms involved in the pathophysiology of insulin resistance, but also to investigate a possible preventive intervention and/or therapy for this pathological condition.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RODRIGUES, HOSANA G.; SATO, FABIO TAKEO; CURI, RUI; VINOLO, MARCO A. R. Fatty acids as modulators of neutrophil recruitment, function and survival. European Journal of Pharmacology, v. 785, p. 50-58, AUG 15 2016. Web of Science Citations: 20.
CORREA, RENAN OLIVEIRA; FACHI, JOSE LUIS; VIEIRA, ALINE; SATO, FABIO TAKEO; VINOLO, MARCO AURELIO R. Regulation of immune cell function by short-chain fatty acids. CLINICAL & TRANSLATIONAL IMMUNOLOGY, v. 5, APR 2016. Web of Science Citations: 159.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.