Faculty of Docosahexaenoic acid (DHA) is a fatty acid that is highly concentrated in brain, cerebral cortex, skin, sperm, testicles and retina. The biochemical pathway for DHA synthesis was enigmatic for a long time and current model suggests that after the series of desaturation and elongation processes in endoplasmic reticulum C24:6n3 is synthesized, transported to the peroxisomal matrix and then shortened to 22:6n-3 via one cycle of β-oxidation followed by its transport back to the endoplasmic reticulum for specific esterification into the appropriate phospholipids.
Deficiency in DHA metabolism could lead to severe diseases in humans and animals, from lethal autosomal-recessive to behavioral and learning deficits. Moreover, DHA may play important role in a lot of diseases that are currently under investigation: neurodegenerative, diabetes and diabetic retinopathy, metabolic syndrome and tumor cells apoptosis. In this project, we will investigate the influence of dietary n-3/n-6 ratio and direct DHA supplementation in insulin dependent and non-insulin dependent diabetes mellitus on DHA metabolism, mitochondrial and peroxisomal oxidation and DHA metabolome. Our assumption is to prove that nutritional modulation can override insulin influence on diabetic dyslipidemia which could have profound influence on the treatment of diabetes. Additionally, we will try to find key enzymes of mitochondrial and peroxisomal β-oxidation which could influence DHA metabolism by nutritional modulation. Investigations will be performed on Sprague–Dawley rats which will be randomly divided into groups with different dietary treatments which will consist of different n3/n6 ratios and increased DHA content. Induction of diabetes will be performed by streptozotocin (IDDM) or by dietary treatment with high fructose/high fat diet (NIDDM). Integration of results from experiment 1 and 2 will define the behaviour of DHA in different types of diabetes. Investigations on subcellular level will allow us to determine the influence of diabetes on peroxisomal and mitochondrial beta oxidation and DHA metabolism. Investigation of DHA metabolome will link nutrition, diabetes and bioactive DHA products. Finally, data from the whole project will result in integration of gained knowledge and better understanding of DHA biosynthesis.