Role of NAD(P)+ transhydrogenase (NNT) in hypothalamic inflammation and brown adipose tissue biogenesis in mice

• Grant number: 23/06469-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2023
• Effective date (End): March 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Roger Frigério Castilho
• Grantee: Ericka Francislaine Dias Costa
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases, AP.TEM

Abstract

The mitochondrial transmembrane protein NAD(P)+ transhydrogenase (NNT) catalyzes the transfer of a hydride between NAD(H) and NADP(H), coupled with the transport of a proton between the intermembrane space and the mitochondrial matrix. This process can occur in the direction of generation of NADPH or NADH (i.e., direct and reverse reactions). The NADPH generated by NNT activity stands out for providing reducing power to peroxide detoxification systems and for participating in anabolic reactions. The expression of Nnt, although ubiquitous, varies greatly among tissues. This fact may be related to the distinct physiological demands of specific tissues. Critical roles of NNT in inflammatory processes have been revealed in recent studies that evaluated mouse macrophages. It is possible that the specific metabolic phenotype of pro-inflammatory M1 macrophages (i.e., respiratory suppression and increased glycolysis) unfavorably affects the supply of mitochondrial NADPH from non-NNT sources. As a result, NNT becomes a unique regulator of immune responses involving redox balance in these cells. The present Project aims to highlight the role of NNT in hypothalamic inflammation and brown adipose tissue biogenesis. Hypothalamic inflammation will be evaluated in Nnt+/+ and Nnt-/- mice chronically treated with a high-fat diet. The importance of NNT in brown adipose tissue biogenesis will be studied in mice and cultured WT-1 brown preadipocytes. The development of this Project may contribute to a better understanding of the role of NNT in inflammatory processes and metabolic control.