Discovery and characterization of food bioactive compounds modulating the Pentose Phosphate Pathway against non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults, and at present there is no approved licensed medication. Oxidative stress has been recognised as an important factor in the pathological progression of NAFLD. Therefore, therapies to protect against liver redox imbalance in the progression of this disease are urgently needed. G6PD is the rate-limiting enzyme of the pentose phosphate pathway (PPP), providing the majority of the cellular NADPH necessary for most antioxidant enzymes. The host group is specialized in nutritional interventions, metabolism and associated pathologies. They have recently demonstrated that increased levels of NADPH, induced by a moderate and regulated overexpression of G6PD, protected against aging-associated ROS oxidative damage in mice. This, in combination with the experience of the applicant in the prevention of NAFLD by using bioactives compounds, create an outstanding context for the Action. This new Marie-Skłodowska-Curie Action will explore the role of G6PD in the prevention or treatment of NAFLD. Technically, a new high-throughput screening platform will be set up to discover and characterise new food bioactive compounds modulating G6PD activity. The new bioactive compounds, as well as previously characterized pharmacological agonists/antagonists of G6PD, will be tested and validated in mouse models of NAFLD, and the mechanisms of action will be assessed using different in vitro and in vivo approaches. This Action will give further insight into the novel concept of the role of the PPP in the field of metabolic diseases, almost unexplored up to date. In addition, it will encompass a very inter-disciplinary approach including the fields of Food Science and Technology, Biomedicine and Molecular Biology, establishing collaborations with different research groups. In all, this Action will constitute a conceptual advance in the field, and will become an optimal scenario for the career development of the applicant.