Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase Influence of Exercise Training

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Justin D.,Dubis,Gabriel S.,Yan,Huimin,White,Joseph D.,Nel La Favor (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Objective-”The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) onmicrovascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention onalleviating obesity-associated dysfunctionality.Approach and Results-”Young, sedentary men and women were divided into lean (body mass index 18--25; n=14),intermediate (body mass index 28--32.5; n=13), and obese (body mass index 33--40; n=15) groups. A novel microdialysistechnique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralisof obese compared with both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis viathe microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascularendothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase inhibitor, lowered (normalized)H2O2 and superoxide levels, and reversed microvascular endothelial dysfunction in obese subjects. After 8 weeks ofexercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects wasrestored to levels similar to lean subjects. Skeletal muscle protein expression of the NADPH oxidase subunits p22phox,p47phox, and p67phox was increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuatedby exercise training in obese subjects.Conclusions-”This study implicates NADPH oxidase as a source of excessive ROS production in skeletal muscleof obese individuals and links excessive NADPH oxidase--derived ROS to microvascular endothelial dysfunction inobesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladi

Additional Information

Publication

Other

Language: English

Date: 2016

Keywords

acetylcholine hydrogen peroxide microdialysis obesity superoxide

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