title: The mitochondrial-targeted antioxidant MitoQ ameliorates metabolic syndrome features in obesogenic diet-fed rats better than Apocynin or Allopurinol.
abstract: 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.
authors: INRA, UMR 866 (Dynamique Musculaire & Métabolisme) , Place Viala, Montpellier , France.
authors: Christine
authors: C
authors: Feillet-Coudray
authors: Gillen
authors: G
authors: Fouret
authors: Raymond
authors: R
authors: Ebabe Elle
authors: Jennifer
authors: J
authors: Rieusset
authors: Beatrice
authors: B
authors: Bonafos
authors: Beatrice
authors: B
authors: Chabi
authors: David
authors: D
authors: Crouzier
authors: Kamelija
authors: K
authors: Zarkovic
authors: Neven
authors: N
authors: Zarkovic
authors: Jeanne
authors: J
authors: Ramos
authors: Eric
authors: E
authors: Badia
authors: Michael P
authors: MP
authors: Murphy
authors: Jean Paul
authors: JP
authors: Cristol
authors: Charles
authors: C
authors: Coudray
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects*; D009765:Obesity; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone; D000493:Allopurinol; C056165:acetovanillone
keywords: MitoQ; NADPH oxidase; antioxidants; free radicals; hepatic steatosis; high fat diet; insulin resistance; metabolic syndrome; mitochondria; obesity; oxidative stress; xanthine oxidase