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
• Start date: August 01, 2020
• End date: 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 research grant(s): 24/09785-5 - Towards understanding the effects of bile acids on the endocrine pancreas: from health to obesity and double burden of malnutrition., AP.R SPRINT; 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): 24/10960-6 - Molecular and functional analysis of the production, secretion, and action of glucagon-like peptide 1 (GLP-1) on pancreatic ²-cell function in double burden of malnutrition, BP.PD; 24/15123-5 - MOLECULAR AND FUNCTIONAL CHARACTERIZATION OF THE ROLE OF alpha5beta1 INTEGRIN RECEPTOR IN HEPATIC DYSFUNCTION DURING AMINO ACID RESTRICTION, BP.IC; 24/09075-8 - Evaluation of the effects of Tauroursodeoxycholic Acid (TUDCA) on energy homeostasis and morphofunction of brown adipose tissue in mice subjected to protein restriction and fed a high-fat diet., BP.IC; + associated scholarships 23/11238-0 - Characterization of potential molecular targets to metabolic dysfunction induced by aminoacids restriction, BP.PD; 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; 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)

Scientific publications

(9)

(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)

DOS REIS ARAUJO, THIAGO; DAVEL, ANA PAULA; CARNEIRO, EVERARDO MAGALHAES. Life-long health consequences of undernutrition in the Yanomami indigenous population in Brazil. Nature Medicine, v. 30, n. 7, p. 2-pg., 2024-04-30. (18/26080-4)

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, APR 12 2021. (18/26080-4, 14/09532-8, 14/01717-9, 13/07607-8)

DE GOUVEA FERNANDES, ANA CLARA; MAGALHAES CARNEIRO, EVERARDO. Technology-Mediated Learning in Higher Education Physiology Classes: The Use of MeGli App to Teach Glycemic Control. PHYSIOLOGY, v. 39, p. 2-pg., 2024-05-01. (18/26080-4, 13/07607-8)

SOARES, GABRIELA M.; BALBO, SANDRA L.; BRONCZEK, GABRIELA A.; VETTORAZZI, JEAN F.; MARMENTINI, CARINE; ZANGEROLAMO, LUCAS; VELLOSO, LICIO A.; CARNEIRO, EVERARDO M.. Vertical sleeve gastrectomy improves glucose-insulin homeostasis by enhancing β-cell function and survival via FGF15/19. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 326, n. 2, p. 14-pg., 2024-02-20. (13/07607-8, 19/00728-0, 18/26080-4)

DE OLIVEIRA, K. M.; ALVES, B. L.; SILVA JUNIOR, J. A.; SOARES, G. M.; MOUSOVICH-NETO, F.; RIBEIRO, R. A.; CARNEIRO, E. M.. Effects of protein restriction on glucose tolerance and large intestine morphofunction in C57Bl/6 mice. Diabetologia, v. 65, n. SUPPL 1, p. 1-pg., 2022-09-01. (18/26080-4, 20/03956-1, 13/07607-8)

SIMOES, BRUNA EDUARDA SANTOS; MUNIZ, MARIANA ROBERTA RODRIGUES; ARAUJO, THIAGO DOSREIS; MAGALHAES CARNEIRO, EVERARDO; SIMIONATO, ANA VALERIA COLNAGHI. Evaluation of tauroursodeoxycholic acid in liver cells' cultures by MEKC: Initial hints to comprehend its role in diabetes mellitus of obese individuals. ELECTROPHORESIS, v. 45, n. 13-14, p. 13-pg., 2024-05-22. (18/26080-4)

LAZARO, C. M.; FREITAS, I. N.; NUNES, V. S.; GUIZONI, D. M.; VICTORIO, J. A.; OLIVEIRA, H. C. F.; DAVEL, A. P.. Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue. FUNCTION, v. 5, n. 4, p. 13-pg., 2024-07-11. (13/07607-8, 17/17728-8, 20/09799-5, 18/26080-4, 19/15164-5, 19/13862-7)

FREITAS, ISRAELLE NETTO; DA SILVA JR, JOEL ALVES; DE OLIVEIRA, KENIA MORENO; ALVES, BRUNA LOURENCONI; ARAUJO, THIAGO DOS REIS; CAMPOREZ, JOAO PAULO; CARNEIRO, EVERARDO MAGALHAES; DAVEL, ANA PAULA. Insights by which TUDCA is a potential therapy against adiposity. FRONTIERS IN ENDOCRINOLOGY, v. 14, p. 8-pg., 2023-02-21. (18/26080-4, 20/05146-7, 19/15164-5)

ARAUJO, THIAGO DOS REIS; MUNIZ, MARIANA ROBERTA RODRIGUES; ALVES, BRUNA LOURENCONI; DOS SANTOS, LOHANNA MONALI BARRETO; BONFIM, MARESSA FERNANDES; DA SILVA JUNIOR, JOEL ALVES; VETTORAZZI, JEAN FRANCIESCO; ZOPPI, CLAUDIO CESAR; CARNEIRO, EVERARDO MAGALHAES. Tauroursodeoxycholic acid improves glucose tolerance and reduces adiposity in normal protein and malnourished mice fed a high-fat diet. Food Research International, v. 156, p. 13-pg., 2022-06-01. (18/26080-4, 17/24851-0)