Red Grape Juice Polyphenols Alter Cholesterol Homeostasis and Increase LDL-Receptor Activity in Human Cells In Vitro

Abstract

Red grape juice (RGJ) polyphenols have been shown to reduce circulating levels of LDL cholesterol and to increase LDL receptor activity. To explore the effect of RGJ-derived polyphenols on intracellular cholesterol homeostasis, human hepatocarcinoma HepG2 and promyelocytic HL-60 cell lines were incubated in serum-free medium, with or without LDL, in the presence or absence of RGJ. In the presence of LDL, RGJ increased both the activity and cell surface expression of the LDL receptor, and increased the cell total cholesterol content. In cells exposed to LDL, RGJ also increased levels of the active form of sterol regulatory element-binding protein-1 and mRNA expression of the LDL receptor and hydroxymethylglutaryl-CoA reductase. In contrast, RGJ caused a marked reduction in the expression of CYP7A1, apolipoprotein B, ABCA1, and ABCG5. Experiments using the acyl-CoA cholesterol acyltransferase inhibitor S-58035 indicated that no measurable free cholesterol from endocytosed LDL reaches the endoplasmic reticulum in cells treated with RGJ. Finally, fluorescence microscopy revealed that in RGJ-treated cells, DiI-labeled LDL did not colocalize with CD63, a protein localized at steady state in the internal vesicles of late endosomes. These results indicate that RGJ polyphenols disrupt or delay LDL trafficking through the endocytic pathway, thus preventing LDL cholesterol from exerting regulatory effects on intracellular lipid homeostasis.

Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men

“…Interestingly, a significant positive correlation between the phenolic content in the oil and linoleic acid-rich moieties was observed. This phenomenon was associated with a possible effect of phenolics on the modulation of the gene and protein expression or activities of key enzymes involved in TG transport and metabolism, like LPL [18], apo B48, microsomal TG transfer protein (MTP) [19], or receptors involved in the uptake of VLDL by the liver [20].…”

Phenolic Compounds and Antioxidant Activity in Grape Juices: A Chemical and Sensory View

“…Several clinical studies on grapes and their derivatives have demonstrated these properties, including protection against cardiovascular diseases [68,69], atherosclerosis [70], hypertension [71], cancer [72], diabetes [73] and neurological problems [74]. The mechanism of action has been attributed to antioxidant activity [75], lipid regulation [76,77], anti-inflammatory effects [78], anti-cancer, antimicrobial, antiviral, cardio protective, neuroprotective, and hepatoprotective activities [1,40,41,48,[79][80][81][82][83].…”

Effects of red grape juice polyphenols in NADPH oxidase subunit expression in human neutrophils and mononuclear blood cells

“…Concentrated RGJ from the 'bobal' grape variety was purchased from Dream Fruits (Quero, Toledo, Spain) containing 6·4 g total polyphenols/l (gallic acid equivalents), 124 mg anthocyanidines/l and a high concentration of flavonoids, including quercetin, myricetin and traces of (2 )-epicatechin, (þ)-catechin, resveratrol and other phenolic acids; a detailed phenolic composition is described elsewhere (30,36) . Red wine from the Tempranillo variety (kindly provided by María de Maeseneire) was used to prepare dealcoholised red wine (DRW).…”