Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients

Marie Hokayem (1) , Emilie Blond , Hubert Vidal (2) , Karen Lambert (1) , Emmanuelle Fouilloux-Meugnier (2) , Christine Feillet Coudray (3) , Charles Coudray (3) , Sandra Pesenti , Cedric Luyton , Stephanie Lambert-Porcheron , Valérie Sauvinet (2) , Christine Fedou (1, 4) , Jean-Frédéric Brun (1, 4) , Jennifer Rieusset (2) , Catherine Bisbal (1) , Ariane Sultan (1, 4) , Jacques Mercier (1, 4) , Jöelle Goudable (2) , Anne-Marie Dupuy (5) , Jean-Paul Cristol (1, 4) , Martine Laville (2) , Antoine Avignon (1, 4)

1 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
2 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
3 DMEM - Dynamique Musculaire et Métabolisme
4 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
5 Lab Biochim

OBJECTIVE-To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS-Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS-In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid-reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS-A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Mots clés: MITOCHONDRIAL DYSFUNCTION; HEPATIC STEATOSIS; METABOLIC DISEASES; RATS; WINE CONSUMPTION; SKELETAL-MUSCLE; HUMANS; DIET; GENE-EXPRESSION; MICE

Domaines: Sciences du Vivant [q-bio]

Marie Hokayem, Emilie Blond, Hubert Vidal, Karen Lambert, Emmanuelle Fouilloux-Meugnier, et al.. Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients. Diabetes Care, 2013, 36 (6), pp.1454 - 1461. ⟨10.2337/dc12-1652⟩. ⟨hal-01837559⟩