Effect of tributyrin, pro-drug of butyrate, on insulin resistance associated to obesity

Abstract

Obesity represents a serious public health problem. This pathological condition is associated with high morbidity and mortality, which is explained by its association with chronic diseases such as hypertension, dyslipidemia and type 2 diabetes mellitus (DM2). Obesity promotes a low-grade chronic inflammatory state, which is involved in dysfunction of various organs and tissues such as pancreas, skeletal muscle and liver. On the other hand, short chain fatty acids, particularly, butyrate, have important anti-inflammatory effects. In this project, we aim to investigate the effect of supplementation with tributyrin, a prodrug of butyrate, on the inflammatory state and the development of insulin resistance in murine obesity models. High-fat feeding C57BL/6 mice and ob /ob mice (leptin-deficient, genetically obese) will be used in the present study. Animals will be treated with tributyrin (2 g/kg body weight) or water by gavage for 10 weeks. After this period, insulin responsiveness will be determined by ITT and analysis in isolated skeletal muscle (glucose metabolism and insulin signaling pathway activation). Production of inflammatory mediators by macrophages and white adipose tissue and the activation of inflammatory pathways in the liver, skeletal muscle and adipose tissue will also be analyzed. The results of this project are not only important for understanding the mechanisms involved in the pathophysiology of insulin resistance, but also to investigate a possible preventive intervention and/or therapy using butyrate. (AU)