The mitochondrial-targeted antioxidant MitoQ ameliorates metabolic syndrome features in obesogenic diet-fed rats better than Apocynin or Allopurinol
2014
Feillet Coudray, Christine | Fouret, Gilles | Ebabe Elle, Etienne Raymond | Rieusset, Jennifer | Bonafos, Béatrice | Chabi, Béatrice | Crouzier, David | Zarkovic, Kamelija | Zarkovic, Neven | Ramos, Jeanne | Badia, Eric | Murphy, Michael P. | Cristol, Jean-Pierre | Coudray, Charles | Dynamique Musculaire et Métabolisme (DMEM) ; Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM) | Nutrition et Alimentation des Populations aux Suds (NutriPass) ; Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro) | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN) ; Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon) ; Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Unité BCM, Institut de Recherches Biomédicale des Armées ; Centre de Recherche du Service de Santé des Armées | Division of Pathology, Medical School, Clinical Hospital Centre ; University of Zagreb | Laboratory for Oxidative Stress ; Rudjer Boskovic Institute [Zagreb] | Laboratoire d’Anatomie Pathologique, CHU Gui de Chauliac ; Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) | MRC Mitochondrial Biology Unit ; University of Cambridge [UK] (CAM) | Free Radicals in Chemical Biology (CHEMBIORADICAL) EU project [CM0603]
The prevalence of metabolic syndrome (MetS) components including obesity, dyslipidemia, insulin resistance (IR), and hepatic steatosis is rapidly increasing in wealthy societies. It is accepted that inflammation/oxidative stress are involved in the initiation/evolution of the MetS features. The present work was designed to evaluate the effects of three major cellular ROS production systems on obesity, glucose tolerance, and hepatic steatosis development and on oxidative stress onset. To do so, 40 young male Sprague-Dawley rats were divided into 5 groups: 1-control group, 2-high fat (HF) group (60% energy from fat), 3-HF + MitoQ (mitochondrial ROS scavenger), 4-HF + Apocynin (NADPH oxidase inhibitor), 5-HF + Allopurinol (xanthine oxidase inhibitor). After 8 weeks of these treatments, surrogate MetS, mitochondrial function, and oxidative stress markers were measured in blood and liver. As expected, rats that were fed the HF diet exhibited increased body weight, glucose intolerance, overt hepatic steatosis, and increased hepatic oxidative stress. The impacts of the studied ROS inhibitors on these aspects of the MetS were markedly different. MitoQ showed the most clinically relevant effects, attenuating body weight gain and glucose intolerance provoked by the HF diet. Both Apocynin and Allopurinol showed limited effects suggesting secondary roles of xanthine oxidase (XO) or NADPH oxidase-dependent ROS production in the onset of oxidative stress-dependent obesity, glucose intolerance, and hepatic steatosis process. Thus, MitoQ revealed the central role of mitochondrial oxidative stress in the development of MetS and suggested that mitochondria-targeted antioxidants may be worth considering as potentially helpful therapies for MetS features.
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