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

Project description

An enzyme to fight liver disease

Increasing incidence of obesity and type II diabetes has contributed to a very high prevalence of non-alcoholic fatty liver disease (NAFLD), an untreatable condition. Now affecting one in four people in Europe, NAFLD can progress to liver cirrhosis and liver cancer. It is also associated with a greater risk of cardiovascular diseases and other malignancies. There is a naturally occurring enzyme in the body that may play a role in halting disease progression. Food-PPP-NAFLD is using high-tech methods to investigate novel bioactive food compounds and previously identified pharmacological agents that boost this molecule's activity. Research outcomes will add new knowledge on the biochemical pathways involved in metabolic diseases.

Objective

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.

Coordinator

FUNDACION IMDEA ALIMENTACION
Net EU contribution
€ 172 932,48
Address
PABELLON CENTRAL DEL ANTIGUO HOSPITAL DE CANTOBLAN EDIFICIO NUMERO 7- CARRETERA MADRID- COLMENAR VIEJO--KILOMETRO 14
28049 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost
€ 172 932,48