The present study addressed the ability of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFA), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to ameliorate liver protein damage derived from oxidative stress and induced by consumption of high-caloric diets, typical of Westernized countries.

The experimental design included an animal model of Sprague-Dawley rats fed high-fat high-sucrose (HFHS) diet supplemented with ω-3 EPA and DHA for a complete hepatic proteome analysis to map carbonylated proteins involved in specific metabolic pathways.

Results showed that the intake of marine ω-3 PUFA through diet significantly decreased liver protein carbonylation caused by long-term HFHS consumption and increased antioxidant system.

Fish oil modulated the carbonylation level of more than twenty liver proteins involved in critical metabolic pathways, including lipid metabolism (e.g., albumin), carbohydrate metabolism (e.g., pyruvate carboxylase), detoxification process (e.g., aldehyde dehydrogenase 2), urea cycle (e.g., carbamoyl-phosphate synthase), cytoskeleton dynamics (e.g., actin), or response to oxidative stress (e.g., catalase) among others, which might be under the control of diet marine ω-3 PUFA.

Fish oil

In parallel, fish oil significantly changed the liver fatty acid profile given by the HFHS diet, resulting in a more anti-inflammatory phenotype. In conclusion, the present study highlights the significance of marine ω-3 PUFA intake for the health of rats fed a Westernized diet by describing several key metabolic pathways which are protected in the liver.

The present study focused on the identification of a pattern for molecular alterations presented under the HFHS diet framework and early stages of oxidative damage.

It provided evidence of the effect of fish oils to reduce the liver protein carbonylation and pro-inflammatory phenotype, as well as the enhancement of the endogenous antioxidant system. Marine ω-3 PUFA consumption led to the specific protection of liver proteins as well.

This different susceptibility of proteins to be oxidized together with the fact that carbonylation did not depend on the concentration of the protein, support the lack of randomness of protein oxidation being more than a mere reflection of ROS levels. There were highly abundant proteins without any carbonylation, or very negligible, coexisting with low concentrated but extremely carbonylated proteins.

Another fact that emphasized the specificity of the carbonylation resides on the different behavior found over some liver proteins, which were found with lower levels of carbonylation after supplementation with EPA and DHA, demonstrated a selective capacity of response of the hepatic proteome to the protection of carbonylation exerted by marine lipids.

The identification of the target carbonylation proteins on which marine ω-3 PUFA exerted a significant effect, allowed the identification of pathways potentially modulated by these acids.