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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

Grant number: 18/26080-4
Support Opportunities:Research Projects - Thematic Grants
Duration: August 01, 2020 - July 31, 2025
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Everardo Magalhães Carneiro
Grantee:Everardo Magalhães Carneiro
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Pesquisadores principais:
Ana Paula Couto Davel
Associated researchers:Aline Mara dos Santos ; Licio Augusto Velloso ; Mariana Sarto Figueiredo
Associated grant(s):23/01509-6 - Characterization of the molecular and functional mechanisms involved in hypothalamic dysfunctions induced by amino acid restriction in vitro and in vivo: possible protective role of the bile acid TUDCA, AP.R
22/04149-8 - Multi-user equipment approved in grant 18/26080-4: Multi Wire Myograph System, AP.EMU
Associated scholarship(s):23/02152-4 - EVALUATION OF THE CONTRIBUTION OF MITOCHONDRIA-ASSOCIATED MEMBRANES (MAMs) IN THE DEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) DURING UNDERNUTRITION: THERAPEUTIC POTENTIAL OF TUDCA, BP.PD
23/01444-1 - Training in Research Laboratory Techniques in Endocrine Pancreas Metabolism., BP.TT
22/04147-5 - Effects of the double burden of malnutrition in endothelial cell function and pancreatic islet vascularization, BP.DR
+ associated scholarships 22/11210-5 - TRAINING IN RESEARCH LABORATORY TECHNIQUES IN ENDOCRINE PANCREAS METABOLISM, BP.TT
21/02734-8 - In vitro and in vivo analysis of the mechanism of action of Tauroursodeoxycholic Acid (TUDCA) on the pancreatic alpha cell morphofunction and on the glucagon counter-regulatory response in a model of malnutrition associated with obesity., BP.DR
21/12226-0 - Training in research laboratory techniques in endocrine pancreas metabolism, BP.TT
21/04217-0 - Training in research laboratory techniques in endocrine pancreas metabolism, BP.TT - associated scholarships

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)

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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)
GARCIA-AREVALO, MARTA; LORZA-GIL, ESTELA; CARDOSO, LEANDRO; BATISTA, THIAGO MARTINS; ARAUJO, THIAGO REIS; FERREIRA RAMOS, LUIZ ALBERTO; AREAS, MIGUEL ARCANJO; NADAL, ANGEL; CARNEIRO, EVERARDO MAGALHAES; DAVEL, ANA PAULA. Ventricular Fibrosis and Coronary Remodeling Following Short-Term Exposure of Healthy and Malnourished Mice to Bisphenol A. FRONTIERS IN PHYSIOLOGY, v. 12, . (18/26080-4, 14/09532-8, 14/01717-9, 13/07607-8)

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