Journal article
Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase: Influence of Exercise Training
Arteriosclerosis, thrombosis, and vascular biology, Vol.36(12), pp.2412-2420
12/2016
DOI: 10.1161/ATVBAHA.116.308339
PMCID: PMC5123754
PMID: 27765769
Abstract
The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality.
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 microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H
O
) and superoxide levels in the vastus lateralis of obese compared with both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase inhibitor, lowered (normalized) H
O
and superoxide levels, and reversed microvascular endothelial dysfunction in obese subjects. After 8 weeks of exercise, H
O
levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the NADPH oxidase subunits p22
, p47
, and p67
was increased in obese relative to lean subjects, where p22
and p67
expression was attenuated by exercise training in obese subjects.
This study implicates NADPH oxidase as a source of excessive ROS production in skeletal muscle of obese individuals and links excessive NADPH oxidase-derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies.
Details
- Title: Subtitle
- Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase: Influence of Exercise Training
- Creators
- Justin D La Favor - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.). jlafavo3@jhmi.eduGabriel S Dubis - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.)Huimin Yan - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.)Joseph D White - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.)Margaret A M Nelson - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.)Ethan J Anderson - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.)Robert C Hickner - From the Human Performance Laboratory, Departments of Kinesiology (J.D.L.F., G.S.D., H.Y., J.D.W., R.C.H.), Pharmacology and Toxicology (M.A.M.N., E.J.A.), Physiology (R.C.H.), East Carolina Diabetes and Obesity Institute (J.D.L.F., M.A.M.N., E.J.A., R.C.H.), Center for Health Disparities (R.C.H.), East Carolina University, Greenville, NC; Department of Urology, The James Buchannan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD (J.D.L.F.); Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City (E.J.A.); and Department of Biokinetics, Exercise and Leisure Science, University of KwaZulu-Natal, Durban, South Africa (R.C.H.)
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.36(12), pp.2412-2420
- Publisher
- United States
- DOI
- 10.1161/ATVBAHA.116.308339
- PMID
- 27765769
- PMCID
- PMC5123754
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Grant note
- R01 HL122863 / NHLBI NIH HHS R15 HL113854 / NHLBI NIH HHS F32 DK100082 / NIDDK NIH HHS
- Language
- English
- Date published
- 12/2016
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology
- Record Identifier
- 9984065316702771
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