In vitro and in vivo analysis of the mechanism of action of tauroursodeoxycholic acid (TUDCA) on the mitochondrial function of pancreatic islets and insulin-responsive tissues submitted to amino acid restriction in association with fatty acids

Abstract

Malnutrition is a metabolic disorder that affects about 795 million individuals worldwide and is due to the reduction in energy or nutritional intake in a given stage of life. It is known that nutritional deficiency, during development and maturation, causes disturbances in biogenesis and mitochondrial function in different tissues of rodents and humans, leading to imbalance of glycemic control and rupture in energetic homeostasis, predisposing to the development of obesity and type Diabetes Mellitus 2 (DM2) in adulthood. Our laboratory has a solid line of research, using amino acid supplementation, especially taurine and TUDCA, aiming the search for therapeutic targets to treat these disorders. TUDCA, formed from the association of UDCA with taurine, has been shown to increase mitochondrial biogenicity and cell survival, and to reduce reticulum stress in different cell types. In addition, it was observed that administration of TUDCA preserved ²-cell morphofunction, normalizing insulin secretion and increasing the sensitivity of this hormone in both obese and human rodents. However, the therapeutic action of TUDCA has not yet been evaluated in rodents with obesity derived from malnutrition. Therefore, in this project we will characterize the action of TUDCA, in vitro, on mitochondrial function in pancreatic islet and insulin-responsive tissues submitted to amino acid restriction in association with fatty acids. From the characterization of the effective actions of this bile acid, in vitro, we can extrapolate to the in vivo model for the development of a possible therapeutic tool with focus on the control and / or treatment of obesity and comorbidities, when the association between malnutrition and rich diet in fat.