Proteomic analysis of aorta of LDLR^−/− mice given omega‐3 fatty acids reveals modulation of energy metabolism and oxidative stress pathway

Abstract

Long chain omega 3 polyunsaturated fatty acids (LC-n-3PUFAs) exert potent anti-atherosclerotic action but the mechanisms of action at the vascular level remain unclear. The present study used a non-targeted nutrigenomic approach to investigate the modulations of the aortic proteome in atherosclerotic prone mice following DHA supplementation. LDLR À/À male mice received an atherogenic diet (20 weeks) in parallel with daily oral gavages with either oleic acid-rich oil (Control) or a mixture of oils providing 2% of energy as DHA. The overall protein expression was determined by a proteomic approach followed by bioinformatics analysis. In addition, protein oxidative modifications, namely 4-hydroxynonenal (4-HNE) protein adducts, were detected with a specific antibody followed by MS analysis of the identified spots. Nineteen differentially expressed proteins have been identified in the aorta of the DHA group. The top 5 canonical pathways analysis associated all proteins to metabolic pathways and showed that most of them were related to glucose or lipid metabolism. Up-regulation of superoxide dismutase also suggests an impact of DHA supplementation on vascular antioxidant defenses. The analysis of 4-HNE-protein adducts indicated that DHA supplementation did not enhance oxidative modification of proteins with 4-HNE. This study also identified some new proteins with 4-HNE adducts at the aortic level. In summary, DHA supplementation induces significant modifications of aorta proteome which point out the importance of metabolic changes occurring in the vascular tissue in the presence of LC-n-3PUFAs.

Hydroxytyrosol and its complex forms (secoiridoids) modulate aorta and heart proteome in healthy rats: Potential cardio‐protective effects

“…Despite that proteomics represents a novel and promising tool to uncover the mechanisms of action as a response to diet or nutrients, the actual use of this technique in dietary interventions is still rather limited . Regarding proteomics focused on cardiovascular tissues, very few studies have been performed up to now investigating the possible protective effect on diseased animals of food bioactive compounds on the protein expression of aortic tissue testing vitamin E and omega‐3 fatty acids and heart tissue testing resveratrol . Other studies analyzing proteome on diseased cardiovascular tissues , such as calcific aortic valve or infarcted myocardium have reflected important changes in protein induced by disease .…”

Marine Lipids on Cardiovascular Diseases and Other Chronic Diseases Induced by Diet: An Insight Provided by Proteomics and Lipidomics

“…Jourmard-Cubizolles et al [ 28 ] studied a specific oxidative PTM, namely 4-hydroxynonenal (4-HNE) protein adducts derived from PUFA peroxidation. These authors investigated the modulation of the aortic proteome in atherosclerotic prone (LDLR −/− ) mice fed an atherogenic diet supplemented with DHA for 20 weeks.…”

“…Fish oil also showed an important action on proteins implicated in the urea cycle and protein metabolism. Additionally, EPA and DHA demonstrated to act on insulin signaling by modulating proteins such as proteasome system [ 16 , 19 , 20 , 21 , 22 , 23 , 24 , 27 , 28 ].…”

“…Proteomics also found a substantial up-regulation of the antioxidant system in blood/plasma and the rest of tissue analyzed. In fact, fish oil induced higher levels of antioxidant enzymes, ameliorating of endoplasmic oxidative stress and stimulating protein and DNA cellular system repair [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 25 , 27 , 28 ]. Moreover, EPA and DHA altered protein carbonylation levels of specific liver proteins, demonstrating an additional mechanism of protein regulation by marine lipids, which is particularly interesting in the investigation of diseases induced by diet.…”

Nutrigenomic effects of omega‐3 fatty acids

“…The use of nutrigenomics in this field of research is therefore very relevant and it has been successfully applied in different human and animal models. For instance, several comprehensive analyses of nutrigenomics effects of omega‐3 PUFAs have been recently published on human blood mononuclear cells or on different tissues of atherosclerosis‐prone animals which helped to better understand the cardioprotective effects of omega‐3 PUFAs. Briefly, all these studies first show that dietary intervention with omega‐3 PUFAs induces substantial modulation of transcriptome, proteome, lipidome and metabolome.…”