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.

A Mitochondrial-Targeted Coenzyme Q Analog Prevents Weight Gain and Ameliorates Hepatic Dysfunction in High-Fat–Fed Mice

“…We were surprised that although our mitoQ treated, HF-fed mice gained less weight than did control HF mice, no difference was seen in hepatic triglyceride or total fat content. However, while this manuscript was in revision, a report appeared describing the effect of mitoQ on features of the metabolic syndrome in HF-fed rats (Feillet-Coudray et al, 2014). Consistent with our observations, these rats gained less weight than controls but also exhibited no change in liver fat content.…”

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…Therefore, the results strongly suggested that Mito-Q decreased the levels of protein nitration and HIF-1α stabilization, possibly through suppressing the production of ROS/ RNS. These beneficial results suggest that some synthetic antioxidants are far more effective than the untargeted natural antioxidants in neutralizing elevated nitroxidative stress and metabolic syndrome features, as reported (Feillet-Coudray et al, 2014). Because of the recent clinical testing, we expect to see approval of some of these antioxidants in treating oxidative stress-mediated various forms of liver disease.…”

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

“…Further, altered Mitochondrial dynamic and trafficking are also targeted by MitoQ AD and MetS [140,141] Oryzanols, Tocopherols and Tocotrienols…”