Subprodutos de peixe como fonte de novos agentes terapêuticos para doenças cardiometabólicas

The FERDINAND project aims to develop novel therapeutics for cardiometabolic diseases, particularly NAFLD, through the valorization of fish by-products. Specific goals have been outlined to achieve this objective: 1. Extraction of high-yield biologically active lipid and peptide fractions from sardine by-products using green technologies. 2. Isolation of hepatic exosomes to design a new delivery system for peptide and lipid fractions, enhancing their bioavailability and biocompatibility. 3. Validation of their bioactivity in cell models to ensure their capacity to modulate inflammatory responses, lipid accumulation, and glucose uptake. 4. Validation of the most promising therapeutics using a pre-clinical multi-organ-on-a-chip model. Managing food waste in fisheries poses a challenge due to the abundance of by-products. Currently, these by-products are primarily used for feed and fertilizers. However, their high nutritional value presents an opportunity for a new value chain. The main challenge in valorizing fish by-products for therapeutic applications lies in the extraction and purification steps to produce safe and biologically active fractions. To address this challenge, FERDINAND focuses on two specific goals: • The use of green technologies for extracting and purifying lipid and peptide fractions from sardine by-products, reducing the use of organic solvents and potential toxicity. • Encapsulation of purified bioactive fractions using hepatocyte-derived exosomes to enhance bioavailability and biocompatibility. This approach aims to produce more targeted therapeutics. Bioactivity will be assessed using in vitro cell models to evaluate the fractions' ability to reduce lipid accumulation, modulate inflammatory responses, and regulate glucose uptake. Additionally, the most promising strategy will undergo validation using a pre-clinical multi-organ-on-chip model, which mimics physiological conditions and reduces costs and resource requirements. Another goal of FERDINAND is to complement biological validation tests with metabolomics approaches. This strategy enables the establishment of models to understand the impact on lipid and glucose metabolism without depending exclusively on conventional techniques such as ELISA, qPCR, and Western blot. Moreover, reducing the use of conventional techniques may lower the associated costs of biological validation.