The mitochondrial-targeted antioxidant MitoQ ameliorates metabolic syndrome features in obesogenic diet-fed rats better than Apocynin or Allopurinol

• DOI: 10.3109/10715762.2014.945079
• Publication Date: 2014-07-28T08:21:03Z
• Authors: Christine Feillet...; Gillen Fouret; Raymond Ebabe Elle; Jennifer Rieusset; Beatrice Bonafos; Beatrice Chabi; David Crouzier; Kamelija Zarkovic; Neven Zarkovic; Jeanne Ramos; Eric Badia; Michael P. Murphy; Jean Paul Cristol; Charles Coudray
• Keywords: Male; obesity; Ubiquinone; MitoQ; Antioxidants; Rats, Sprague-Dawley; oxidative stress; Metabolic Syndrome; 2. Zero hunger; 0303 health sciences; syndrome métabolique; Reverse Transcriptase Polymerase Chain Reaction; hepatic steatosis; high fat diet; metabolic x syndrome; [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism; Mitochondria; 3. Good health; mitochondria; obésité; antioxidants; mitochondrie; insulin; Allopurinol; Blotting, Western; 610; free radicals; nadph oxydase; Diet, High-Fat; Real-Time Polymerase Chain Reaction; metabolic syndrome; resistance; liver steatosis; 03 medical and health sciences; Organophosphorus Compounds; stéatose hépatique; antioxidants; free radicals; hepatic steatosis; high fat diet; insulin resistance; metabolic syndrome; mitochondria; MitoQ; NADPH oxidase; obesity; oxidative stress; xanthine oxidase; 616; Animals; Obesity; résistance à l'insuline; NADPH oxidase; stress oxydatif; Acetophenones; Rats; Disease Models, Animal; Oxidative Stress; espèce reactive de l'oxygène; xanthine oxidase

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.