INVOLVEMENT OF THE VAGUS NERVE AND HYPOTHALAMIC REGULATORS IN ENERGY HOMEOSTASIS IN OBESE MICE

• Grant number: 23/13857-9
• Support Opportunities: Research Grants - Visiting Researcher Grant - Brazil
• Start date: April 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Antonio Carlos Boschiero
• Visiting researcher: Rodrigo Mello Gomes
• Visiting researcher institution: Instituto De Ciências Biológicas/Icb/Ufg, Brazil
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/04664-7 - Molecular mechanisms involved in pancreatic beta cell dysfunction and death in Diabetes Mellitus: strategies for the inhibition of these processes and restoration of the insular mass, AP.TEM

Abstract

The Autonomic Nervous System (ANS) performs numerous regulatory functions, among which we can highlight its role in the release of insulin by pancreatic beta cells. The parasympathetic subdivision (PNS) of the ANS represented by the vagus nerve has afferent and efferent fibers enabling the traffic of information from the periphery to the central nervous system (CNS) and vice versa. The action of PNS on pancreatic beta cells promotes an insulinotropic effect when Ach binds to cholinergic receptors of the M3 subtype. It has been observed that in obese animals there is an increase in the electrical activity of the vagus nerve, corroborated by greater expression of M3 in the islets and elevated insulin secretion, under basal conditions, stimulated by glucose and selective cholinergic agonists for M3. However, many gaps remain, including the role of the nodose ganglion on the action of the vagus nerve on insulin secretion and the effect of obesity induced by high-fat diets on inflammation in the nodose ganglion and the metabolic implications within this scenario. The main objective of this project, with the contribution of the visiting researcher, will be to evaluate the role of stimulation and inhibition of the vagus nerve in mice with a lean or obese phenotype, as well as its metabolic effects. The influence of the hypothalamic and nodose ganglion inflammatory state will also be evaluated. We will verify the contribution of total and selective subdiaphragmatic vagotomy on the inflammatory profile in CNS centers. Finally, we will evaluate the central effects of FGF19 administration in the face of hypothalamic dysregulation, and the effects of intracerebroventricular (ICV) irisin administration in modulating microglial and hypothalamic neuroinflammation. (AU)