Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer’s Disease

Long-term fish oil (FO) supplementation is able to improve Alzheimer’s disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice. Livers of both genotypes responded by increase of n-3 and reciprocal decrease of n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver correlation exists only for n-6 fatty acids. Expression of omega-3 transporter Mfs2a remained unchanged after FO supplementation. We have demonstrated that even a short-term FO intake improves the phospholipid composition and has a significant effect on plaque burden in 5xFAD brains when applied in early stages of AD pathology.