Characterization of molecular and functional mechanisms involved in endocrine-metabolic, cardiovascular and neural dysfunctions induced by the restriction of amino acids in vitro and in vivo: possible therapeutic role of bile acid TUDCA

Abstract

Malnutrition still affects thousands of people around the world. In addition to the deaths, malnutrition during the early stages of life compromises the development of organs and tissues essential to the maintenance of glycemic, lipid and energetic metabolism. Reprogramming of such organs and tissues may lead to metabolic changes that increases susceptibility to the development of pathological processes such as Obesity and Diabetes in adult life. In this sense, both the endocrine pancreas responsible for secreting insulin and glucagon, as well as organs responsive to these hormones undergo such reprogramming induced by malnutrition, including the cardiovascular system. In addition, hypothalamus, brown adipose tissue and thyroid, which play a fundamental role in energy metabolism, also present dysfunctions in the face of early malnutrition, impairing energy metabolism. Bile acids have been highlighted as potential therapeutic agents in the treatment and prevention of such metabolic diseases, since they seems to reestablish the glycemic, lipid and energetic metabolism through the activation of membrane and intracellular receptors. Recent studies show that, under conditions of Obesity and Diabetes, the bile acid tauroursodeoxycholic (TUDCA) acts directly on pancreatic alpha and beta cells, normalizing serum insulin, glucagon and glucose levels. In addition, TUDCA improves peripheral insulin signaling and regulates energy metabolism in brown adipose tissue. This compound also acts on the hypothalamus, reducing tissue inflammation, and vascular endothelial cells reducing oxidative stress. However, the possible effects as well as the molecular mechanisms involved in TUDCA signaling in malnutrition models are still poorly understood. Thus, we intend to evaluate the effects of TUDCA in restoring the function of organs and tissues essential to the maintenance of glycemic, lipid and energetic metabolism, as well as the molecular mechanisms involved in this signaling, after exposure to amino acid restriction. (AU)