Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet.

Lucía Méndez,Sara Ramos-Romero,Josep Lluis Torres,Maria Rosa Nogués,Isabel Medina,Bernat Miralles-Pérez,Silvia Muñoz

doi:10.3390/md18010034

Abstract

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases and type 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damage biomolecules, especially proteins. The present study was designed to investigate the effect of marine omega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins from plasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS) diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of protein carbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combination of both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in both plasma and liver. The analysis of carbonylated protein targets, also referred to as the ‘carbonylome’, revealed an individual response of liver proteins to supplements and a modulatory effect on specific metabolic pathways and processes due to, at least in part, the control exerted by the supplements on the liver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grape seed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption of HFHS diets.

Highlights

The consumption of high fat and high sucrose diets leads to obesity, which represents a severe worldwide public health concern in terms of contribution to human diseases
Considering that: (a) Protein carbonylation and obese-derived metabolic alterations are closely related; (b) fish oils [24] and grape seed polyphenols extract (GSE) [25] have separately exerted an effect in modulating protein carbonylation; and (c) the additive effects of fish oils and GSE in several aspects of metabolism already study in the same cohort of rats, such as gut microbiota, regulation of protein expression and lipid mediator profiles [15,20,23]; the present study aimed to explore the effects of ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
Considering firstly total protein carbonylation, we found that the inclusion of marine ω-3 polyunsaturated fatty acids (PUFAs) in the high-fat and high-sucrose (HFHS)

Summary

Introduction

The consumption of high fat and high sucrose diets leads to obesity, which represents a severe worldwide public health concern in terms of contribution to human diseases. Obesity increases the likelihood of developing other serious conditions, including cardiovascular diseases and type 2 diabetes [1]. Mar. Drugs 2020, 18, 34 diseases is critical for the assessment of more appropriate and successful prevention/palliation strategies against metabolic disorders. Chronic oxidative stress results in increased levels of oxidized proteins. This fact can be enough to trigger cellular dysfunction since almost the whole metabolism relies on proteins to execute key cellular processes [4]. Proteins can be modified by several oxidative modifications but protein carbonylation is considered a major hallmark of oxidative damage [5]. Several pieces of information have linked protein carbonylation to obesity and derived diseases [9]. It has been reported that overnutrition induces extensive carbonylation of GLUT4 in adipose tissue, which leads to protein activity loss, and insulin resistance [10]

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Conclusion