Metabolic Fate and Cardiometabolic Effects of Phenolic Compounds from Red‐Fleshed Apple in Hypercholesterolemic Rats: A Comparative Study with Common White‐Fleshed Apple. The AppleCOR Study

Abstract

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red-and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats.

New red-fleshed apple cultivars: a comprehensive review of processing effects, (poly)phenol bioavailability and biological effects

“…Metabolic pathways originating from the major (poly)phenols detected in RFA (chlorogenic acid, vanillic acid hexoside, cyanidin-3- O -galactoside, epicatechin and dimer B 2 , quercetin derivatives and phloretin glucoside) were proposed. The (poly)phenolic metabolic profile described in this study was very similar to those observed in other studies in Wistar rats whose diet was supplemented with RFA 77,78 or in a recent intervention study 79 with hypercholesterolemic subjects who consumed 80 g day −1 of freeze-dried RFA.…”

Red-Fleshed Apples Rich in Anthocyanins and White-Fleshed Apples Modulate the Aorta and Heart Proteome in Hypercholesterolaemic Rats: The AppleCOR Study

“…Moreover, our study, for the first time, provides insights on how apples alter the expression of different CVD related proteins in the rat heart and aorta tissues by a proteome profile analysis. In the frame of this study, our previous work showed cardiometabolic protective effects of both red-fleshed and white-fleshed apples and also aronia infusion supplementation, specifically in the significant reduction of the aorta thickness [ 26 ]. Although no gender differences were observed in this proteomics study, we observed gender differences in some cardiometabolic parameters [ 26 ].…”

“…In the frame of this study, our previous work showed cardiometabolic protective effects of both red-fleshed and white-fleshed apples and also aronia infusion supplementation, specifically in the significant reduction of the aorta thickness [ 26 ]. Although no gender differences were observed in this proteomics study, we observed gender differences in some cardiometabolic parameters [ 26 ]. Specifically, we observed that the kidney function was improved after all supplementations (both apples and aronia) but only in females (probably related to the higher phenol bioavailability reported in females).…”

“…In this sense, the apple phenolic composition contains more than just anthocyanins, and the observed effects may be due to the apple phenolic phytocomplex that could act synergistically to beneficially impact the aorta and heart proteomes. Moreover, our group also recently observed an apple matrix effect between the red-fleshed apple variety and Aronia extract infusion, demonstrating a higher bioavailability and excretion of ACN after Aronia extract infusion supplementation [ 26 ]. The differences observed could be related to the fact that the ACNs in apples are bound to fibre, while in the Aronia extract infusion, the ACNs are more available in their free forms, which favours their gastrointestinal absorption and metabolism.…”

Anthocyanins: From Mechanisms of Regulation in Plants to Health Benefits in Foods

“…The analyses of fecal microbiota and of gene expression in peripheral blood mononuclear cells (PBMC, which consist of peripheral blood cells having a round nucleus, like lymphocytes and monocytes) have shown minimal differences between the two groups, but genes regulated by red-fleshed apples were immunoglobulin-related, suggesting a potential role in modulating the immune function (Barnett et al, 2021). Finally, both red-and white-fleshed apples seemed to have beneficial effects in hypercholesterolemic rats (Yuste et al, 2021) or in model rats with adenocarcinoma (Bars-Cortina et al, 2020). The benefits of apple and anthocyanin consumption are well established (Knekt et al, 2002;Boyer and Liu, 2004;Cassidy et al, 2015Cassidy et al, , 2016Hyun and Jang, 2016), and apples with high anthocyanin contents could offer effective functional foods, to reduce the incidence of chronic diseases when part of a normal diet.…”