Diseases affecting normal fatty acid metabolism can be caused by either nutritional dysregulations or genetic disorders. Traditionally, these disorders have been studied and characterised using animal models. In vivo models not only represent ethical issues, but also translational differences with humans.
In this thesis Jose Horcas Nieto we have demonstrated that in vitro models (specifically organoids, "mini-organs" that resemble the organ of origin) are efficient tools to understand the pathophysiology of the diseases without the need for large numbers of animals. The combined used of in vitro and in silico models allowed us to understand different aspects of the metabolic alterations in malnutrition and Medium-Chain Acyl-CoA dehydrogenase deficiency and how different cellular organelles are involved in these alterations. These platforms have allowed us to shed some light into the role of peroxisomes and mitochondria (organelles involved in fatty acid metabolism within the cell) and their interplay in both malnutrition and MCADD.
Finally, we present the malnutrition model as a tool to not only understand the disease but also to use as a screening tool to test different compounds to prevent peroxisomal loss.
