Fish oil supplementation counteracts the effect of high-fat and high-sucrose diets on the carbonylated proteome in the rat cerebral cortex

High daily intake of saturated fats and refined carbohydrates, which often leads to obesity and overweight, has been associated with cognitive impairment, premature brain aging and the aggravation of neurodegenerative diseases. Although the molecular pathology of obesity-related brain damage is not fully understood, the increased levels of oxidative stress induced by the diet seem to be definitively involved. Being protein carbonylation determinant for protein activity and function and a main consequence of oxidative stress, this study aims to investigate the effect of the long-term high-fat and sucrose diet intake on carbonylated proteome of the cerebral cortex of Sprague-Dawley rats. To achieve this goal, the study identified and quantified the carbonylated proteins and lipid peroxidation products in the cortex, and correlated them with biometrical, biochemical and other redox status parameters. Results demonstrated that the obesogenic diet selectively increased oxidative damage of specific proteins that participate in fundamental pathways for brain function, i.e. energy production, glucose metabolism and neurotransmission. This study also evaluated the antioxidant properties of fish oil to counteract diet-induced brain oxidative damage. Fish oil supplementation demonstrated a stronger capacity to modulate carbonylated proteome in the brain cortex. Data indicated that fish oils did not just decrease carbonylation of proteins affected by the obesogenic diet, but also decreased the oxidative damage of other proteins participating in the same metabolic functions, reinforcing the beneficial effect of the supplement on those pathways. The results could help contribute to the development of successful nutritional-based interventions to prevent cognitive decline and promote brain health.The Spanish Ministry of Science and Innovation is gratefully acknowledged for the doctoral fellowship to Francisco Moreno. Lucía Méndez acknowledges the postdoctoral financial support received from AEI within the Juan de la Cierva Spanish Postdoctoral Program (IJC2020–046017-I/MCIN/AEI/ 10.13039/501100011033 and “NextGenerationEU”/PRTR”) and Xunta de Galicia—Axencia Galega de Innovación (GAIN) (IN606C2021/003). Ana Raner gratefully acknowledge to the EIT Food RIS Fellowships 2020. Bernat Miralles-P é rez acknowledges the postdoctoral financial support received from the Ministry of Universities and the Recovery, Transformation and Resilience Plan funded by the European Union–NextGenerationEU (2021URV-MS-15) and the doctoral financial support received from the Secretariat of Universities and Research of the Government of Catalonia, the European Union, and the European Social Fund (2018 FI_B 00919, 2019 FI_B1 00160, 2020 FI_B2 00119). The authors thank Lorena Barros and Vanessa Sánchez-Martos for their excellent technical assistance. The authors gratefully acknowledge to AFAMSA (Vigo, Spain) for generously provide the fish oils.Peer reviewe