Impact of the NAD+ Synthesis Pathway in Hypothalamic Microglia on the Control Energy Homeostasis

• Grant number: 25/00572-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Eduardo Rochete Ropelle
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Adelino Sanchez Ramos da Silva ; Dennys Esper Corrêa Cintra ; Fernando Moreira Simabuco ; José Rodrigo Pauli

Abstract

Excessive consumption of saturated fat stimulates neuroinflammation and alters the mitochondrial activity in hypothalamic tissue, contributing to increased signals orexigenic and anti-thermogenic, leading to the obese phenotype. In this context, theactivity of the coenzyme nicotinamide adenine dinucleotide (NAD) can be considered a promising therapeutic target, as it has a notable effect onmitochondrial activity, in addition to attenuating the inflammatory process in multiple tissues and under different conditions. Recent studies show that saturated fat impacts negatively on NAD biosynthesis in peripheral tissues such as muscle and liver,However, the effects of saturated fat on NAD synthesis in tissue hypothalamic cells, especially in glial cells, have not yet been fully elucidated.Therefore, the objective of the current project will be to evaluate the effect of saturated fat on the synthesis of NAD+ in microglia, in an experimental model of obesity. Cell-based experiments will be carried out using BV2 cells, a derived microglia cell from rodents, which will be treated with palmitate and then exposed or not to the NAD+ precursor, Nicotinamide Riboside (NR). Mice will be treated with a diet rich in saturated fat supplemented or not with NR. Also, experiments will be carried out involving the overexpression of the Nampt protein (a key enzyme in NAD+ biosynthesis), specifically in the microglia of mice. Physiological tests and molecular biology techniques, including real-time PCR, immunofluorescence, Western blot, RNAseq, among others, will be combined. The development of the current project could promote advances in substantial knowledge about the mechanisms involved in the control of body weight, as well as opening new therapeutic targets to combat obesity. (AU)