Pentose phosphate pathway and serine oxidation fluxes in NAFLD and NASH

Objetivo temático: Develop a polyvalent p-amino benzoic acid (PABA) probe, that in combination with ingested [U-13C]glucose, will noninvasively quantify hepatic G6P flux into PPP and SGO in human subjects

Área Científica: Non-Alcoholic Steatohepatitis; Diabetes and Obesity

Síntese do Projeto: Due to increased obesity rates, the incidence of nonalcoholic fatty liver disease (NAFLD) is also surging. While simple NAFLD is benign, it can progress to non-alcoholic steatohepatitis (NASH) - a more severe and refractory state that can lead to cirrhosis and/or hepatocellular carcinoma. NAFLD is characterized by high rates of de novo lipogenesis (DNL) and elevated oxidative stress (OS). Both DNL and antioxidant activity require NADPH, in part generated by pentose phosphate pathway (PPP) and serine-glycine oxidation (SGO). The higher OS in NASH suggests an imbalance between NADPH supply and demand and loss of NADPH homeostasis. Thus, we hypothesize that NAFLD to NASH progression is associated with altered PPP and SGO fluxes from glucose-6-P (G6P).

Investigador Responsável na UC: John Griffith Jones

Unidade Orgânica UC: Reitoria - CNC

Instituições participantes no Projeto: Universidade de Coimbra

Instituição Financiadora/Gestora: Pfizer Inc.

Programa de Financiamento: Pfizer Global NASH ASPIRE Competitive Grant Program

Período de execução: 01/01/2024 a 31/12/2025 (24 meses)

Custo total elegível (EUR): 130 830,50 € ($ 139 988,66)

Técnico do Projeto: Heidi Maria da Silva Lopes Gonçalves | heidi.goncalves@uc.pt

Contacto: 239247017