Role of hypothalamic NAD+ synthesis pathway in the control of energy homeostasis

• Grant number: 22/08278-7
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2023
• End date: April 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Agreement: National Research Foundation of Korea (NRF)
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Eduardo Rochete Ropelle
• Principal researcher abroad: Dongryeol Ryu
• Institution abroad: Sungkyunkwan University, Seoul (SKKU), South Korea
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Carlos Kiyoshi Katashima

Abstract

The prevalence of overweight and obesity is increasing over the years and one of the main causes is the inappropriate lifestyle including overnutrition and sedentarism. Excessive consumption of saturated fat alters the functionality of hypothalamic cells that control whole-body energy homeostasis. High-fat diets can affect mitochondrial activity in microglia and neurons in the hypothalamus altering control of food intake and energy expenditure in mammals. Recent studies indicate that the reduction of intracellular levels of NAD+ compromise mitochondrial function in several cell types, however the effects of high-fat diet consumption on the production of NAD+ in hypothalamus cells have not been fully elucidated. In this context, the current project will aim to evaluate the role of hypothalamic NAD+ synthesis pathway in the control of energy homeostasis. For this, we will combine experiments involving cell culture, mouse model of obesity and bioinformatics analysis, including machine learning assay using human and mouse transcriptome. The development of the current project may provide new knowledge about the effects of the high-fat diet on NAD+ production and on the functioning of mitochondria in hypothalamic cells, opening new opportunities to prevent or treat obesity. (AU)