ω-3 polyunsaturated fatty acids (PUFAs) are crucial for brain structure and function, especially docosahexaenoic acid (DHA). However, an excess of DHA may increase lipid peroxidation due to its high degree of unsaturation, particularly in tissues highly susceptible to oxidative stress, such as the brain. Therefore, this study evaluated the effects of 10 weeks of dietary supplementation with fish oil containing 80% DHA on oxidative stress and the modulation of the carbonylated proteome in both the cerebral cortex and cerebellum of male Sprague Dawley rats. The results were compared with those induced by oils with a lower degree of fat unsaturation (fish oil containing 25% DHA and 25% eicosapentaenoic acid, soybean oil containing 50% linoleic acid and coconut oil containing 90% saturated fat). The results demonstrated that fish oil containing 80% DHA significantly increased the ω3/ω6 ratio in both the cortex and cerebellum while stimulating antioxidant defense by enhancing the reduced glutathione amount and decreasing the carbonylation of specific proteins, mainly those involved in glycolysis and neurotransmission. The majority of sensitive proteins in both brain regions followed this carbonylation trend (in decreasing order): soybean > EPA/DHA 1:1 > coconut > 80% DHA. The results also indicated that the cerebellum is more responsive than the cortex to changes in the cellular redox environment induced by varying degrees of fat unsaturation. In conclusion, under healthy conditions, dietary supplementation with fish oils containing high DHA levels makes the brain more resilient to potential oxidative insults compared to oils with lower DHA content and a lower degree of fatty acid unsaturation.

This research was funded by the Spanish Ministry of Science and Innovation, grant numbers RTI2018-095659-B-I00 and PID2020–117009RB-I00; the Spanish Ministry of Economy and Competitiveness, grant number AGL2013-49079-C2-1, 2-R; the AEI within the Juan de la Cierva Spanish Postdoctoral Program (IJC2020-046017-I/MCIN/AEI/10.13039/501100011033 and “NextGenerationEU/PRTR”); and the Xunta de Galicia—Axencia Galega de Innovación (GAIN) (IN606C2021/003).

Peer reviewed