Food-PPP-NAFLD · Discovery and characterization of food bioactive compounds modulating the Pentose Phosphate Pathway against non-alcoholic fatty liver disease.
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-10-01 → 2021-09-30
- Финансиране от ЕС
- 172 932 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Биоактивни съединения от храната се тестват за влияние върху метаболитния път „пентоза-фосфат“, за да се намалят възпаленията при неалкохолно мастно дробно заболяване. Това помага за разработването на персонализирана терапия, която отчита разликите в метаболизма между мъжете и жените.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Discovery and characterization of food bioactive compounds modulating the Pentose Phosphate Pathway against non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) epidemic is a public health concern with a severe healthcare burden. It affects about 25% of adults and currently there is no approved pharmacological treatment. In the general adult population, NAFLD prevalence is higher in men than in women. It has been demonstrated that female and male livers are metabolically distinct organs. Despite the current knowledge on the topic, there is no evidence to allow sex-specific personalized therapies. Thus, it is key to identify sex-dependent metabolic pathways in order to address a personalized therapy. Oxidative stress and inflammation have been recognised as important factors in the pathological progression of NAFLD. The accumulation of hepatic lipids derives into oxidative damage, manifested in the liver as an increased lipid peroxidation, which subsequently can result in hepatocyte injury and cell death. This scenario can trigger an inflammatory response and progression to non-alcoholic steatohepatitis (NASH). Therefore, therapies to protect against liver redox imbalance in the progression of this disease are urgently needed. In this regard, the overall objective of this new Marie-SkŁodowska-Curie Action was to dissect the role of the pentose phosphate pathway (PPP) as a therapeutic strategy to prevent oxidative stress and inflammation as the primary target against NASH progression. To achieve this aim, the gender dimension has been considered using both genetic and pharmacological approaches in a mouse diet intervention inducing NASH. In addition, to find new bioactive compounds with the ability to modulate the PPP as pharmacological drugs to treat NASH, a screening was performed. Overall, we have observed that using both the genetic and the pharmacological strategies, females were more protected than males against the oxidative and inflammatory damage induced by the mouse diet intervention inducing NASH. The pharmacological approach reduced more efficiently the NASH liver parameters, including an amelioration of the histological evaluation, the oxidative stress markers and reduction of the liver triglycerides.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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.
Оригинален текст от CORDIS (на английски).
Участници
- FUNDACIÓN IMDEA NUTRICIÓN · MADRIDКоординаторИспания
Връзки
Данни: CORDIS, © Европейски съюз