Targeting Hepatic Protein Carbonylation and Oxidative Stress Occurring on Diet-Induced Metabolic Diseases through the Supplementation with Fish Oils

Abstract

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. 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 liver.

Mitigation with plant ethanol extracts of STZ-induced histopathological injuries in the tissues of laboratory rats

“…The level of protein carbonylation is one of the indexes of protein damage caused by oxidative stress [26]. In our experiments, contrary to the lipid peroxidation, the difference in the protein carbonylation was not registered in any of experimental groups.…”

The Effects of the Combination of Buckwheat D-Fagomine and Fish Omega-3 Fatty Acids on Oxidative Stress and Related Risk Factors in Pre-Obese Rats

“…The decrease in plasma IL-6 in rats receiving the combined supplementation compared to those fed the STD diet might be explained by the distinct fatty acid composition of the dietary backgrounds (STD or HF) and the use of fish oil instead of soybean oil. As we previously reported in the same cohort of rats [32], the STD diet increases the ω-6 PUFA content in the liver compared to the HF diet. The soybean oil is rich in linoleic acid (LA, 18:2 ω-6) (Table S3), which is a precursor of arachidonic acid (ARA, 20:4 ω-6) [55].…”

“…It is well-known that dietary ω-3 PUFA and its oxidized metabolites exert antioxidant effects in humans [ 24 ], probably by activating the nuclear factor-erythroid 2-related factor 2 signaling pathway [ 62 , 63 ]. Indeed, previous studies have shown that ω-3 PUFA supplementation attenuates the increase in the GSSG/GSH ratio and the content of protein carbonyls in the liver induced by excessive fat intake in rodents [ 32 , 38 ], which is accompanied by enhanced insulin sensitivity [ 38 ]. Furthermore, Selenscig et al [ 37 ] have shown that replacing corn oil as a dietary fat source with fish oil improves the epididymal adipose tissue function in rats fed a diet rich in sucrose by increasing antioxidant defenses and reducing ROS production.…”

“…Lipid peroxidation (conjugated dienes hydroperoxides) and total protein carbonylation in plasma and liver were measured as previously described [ 32 ]. Briefly, total lipids were extracted and quantified.…”

Design of Fluorescent Probes for Bioorthogonal Labeling of Carbonylation in Live Cells

“…The increased level of ROS and disturbed redox signaling results in the oxidative damage on biomolecules in living systems. Many disorders which can trigger cancer or metabolic diseases are closely correlated with oxidative stress 3,4 .…”