Analysis of endocrine pancreatic cell plasticity in mice subjected to double burden malnutrition and treated with the bile acid tauroursodeoxycholic acid (TUDCA)

• Grant number: 25/25184-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2026
• End date: December 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Yasmin Simoso Marinelli
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 24/23120-6 - Molecular and functional characterization of endocrine-metabolic, cardiovascular and neurological changes in the double burden of malnutrition: Potential mechanisms of action of Tauroursodeoxycholic Acid (TUDCA), AP.TEM

Abstract

This study addresses the concept of the double burden of malnutrition (DCM), a growing phenomenon in developing countries, closely associated with food insecurity and the consumption of ultra-processed foods. Although childhood undernutrition has decreased in Brazil, the rise in overweight and obesity reflects an unbalanced nutritional transition. DCM increases the risk of metabolic disorders such as hepatic steatosis, type 2 diabetes, and cardiovascular diseases. The endocrine pancreas, responsible for hormonal production (insulin, glucagon, somatostatin, among others), undergoes structural and functional alterations when subjected to DCM. Protein-energy undernutrition impairs the formation of ¿-cells in the islets of Langerhans, reducing insulin secretion and leading to insulin resistance. Subsequent caloric excess promotes lipotoxicity and cellular apoptosis, exacerbating the condition, while epigenetic effects may perpetuate the damage across generations. Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, stands out for its ability to reduce endoplasmic reticulum stress and restore ¿-cell function. Studies indicate that TUDCA improves insulin sensitivity and secretion, promoting plasticity and possible transdifferentiation of ¿-cells into ¿-cells, thereby enhancing pancreatic regenerative capacity. The aim of this project is to evaluate the effects of TUDCA on the reorganization of pancreatic islet cells and the regeneration of ¿-cells in C57Bl/6J mice fed normoproteic, hypoproteic, and high-fat diets, with or without TUDCA treatment. Biochemical and histological parameters will be analyzed, as well as immunofluorescent labeling for insulin, glucagon, and transcription factors (PAX4, Nkx6.1, and PDX1). Preliminary results show that TUDCA restores insulin secretion by ¿-cells and alters the cellular composition of pancreatic islets. In summary, TUDCA may act as a regenerative agent and modulator of pancreatic cell plasticity, offering therapeutic potential against the metabolic effects of DCM. (AU)