Effects of the double burden of malnutrition in endothelial cell function and pancreatic islet vascularization

• Grant number: 22/04147-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2022
• Effective date (End): February 28, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Paula Couto Davel
• Grantee: Leticia Barssotti dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/26080-4 - 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, AP.TEM

Abstract

The term malnutrition refers to deficiencies, excesses, or imbalances in nutrient intake and utilization, and includes both malnutrition and Obesity. Both are risk factors for cardiovascular disease and Diabetes. Proper functioning of the pancreatic islet microvasculature is essential for beta cell endocrine activity and glycemic homeostasis, therefore, strategies for glycemic control should also target vascular dysfunction in islets. Protein restriction in early stages of development impairs the secretory activity of beta cells, and the damage is potentiated by high-fat diet-induced Obesity in adulthood. The coexistence of malnutrition and Obesity throughout life characterizes the double burden of malnutrition, and little is known about its impact on the islet microvasculature and the possible associated mechanisms. Endothelial cells exert important local control of vascular function including regulation of arterial tone, redox and inflammatory status, in addition to capillarization. Thus, we hypothesized that protein restriction in the early stages of postnatal development programs endothelial dysfunction and alterations in the vascularization of the endocrine pancreas, and this damage may be even worse when associated with a high-fat diet in adulthood. We aim to investigate 1) whether the double burden of malnutrition characterized by protein restriction followed by high-fat diet-induced Obesity impacts the reactivity of the pancreatic lieno-resistance artery, the calcium concentration of pericytes and the diameter of islet capillaries; and 2) the in vitro effects of two cardiometabolic risk factors (amino acid restriction and palmitic acid), alone and together, on cell migration and death, nitric oxide (NO) and hydrogen sulfide (H2S) production, and on endothelial cell transcriptome. (AU)