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Cited by 67Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

Crucial roles of N ox2‐derived oxidative stress in deteriorating the function of insulin receptors and endothelium in dietary obesity of middle‐aged mice

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Du, Junjie, Fan, Lampson M, Mai, Anna, Li, Jian‐Mei·2013·British Journal of Pharmacology
DOI 10.1111/bph.12336PMC PMC3949654
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Abstract

Background and Purpose: Systemic oxidative stress associated with dietary calorie overload plays an important role in the deterioration of vascular function in middle‐aged patients suffering from obesity and insulin resistance. However, effective therapy is still lacking. Experimental Approach: In this study, we used a mouse model of middle‐aged obesity to investigate the therapeutic potential of pharmaceutical inhibition (apocynin, 5 mM supplied in the drinking water) or knockout of N ox2, an enzyme generating reactive oxygen species (ROS), in high‐fat diet (HFD)–induced obesity, oxidative stress, insulin resistance and endothelial dysfunction. Littermates of C57BL/6J wild‐type (WT) and N ox2 knockout (KO) mice (7 months old) were fed with a HFD (45% kcal fat) or normal chow diet (NCD, 12% kcal fat) for 16 weeks and used at 11 months of age. Key Results: Compared to NCD WT mice, HFD WT mice developed obesity, insulin resistance, dyslipidaemia and hypertension. Aortic vessels from these mice showed significantly increased N ox2 expression and ROS production, accompanied by significantly increased ERK1/2 activation, reduced insulin receptor expression, decreased A kt and eNOS phosphorylation and impaired endothelium‐dependent vessel relaxation to acetylcholine. All these HFD‐induced abnormalities (except the hyperinsulinaemia) were absent in apocynin‐treated WT or N ox2 KO mice given the same HFD. Conclusions and Implications: In conclusion, N ox2‐derived ROS played a key role in damaging insulin receptor and endothelial function in dietary obesity after middle‐age. Targeting N ox2 could represent a valuable therapeutic strategy in the metabolic syndrome.

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  • Mice carrying NOX2 deletion treated with high fat diet gain weight but show no increase in ROS production or endothelial dysfunction compared with control animals.

    “In these studies, mice carrying the deletion gain weight but show no increase in ROS production or endothelial dysfunction as compared with the control animals (256, 609).”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [256]

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Authors
Du, J., Fan, L. M., Mai, A., & Li, J.
Affiliations
  • University of Surrey (GB)
  • John Radcliffe Hospital (GB)
Corresponding author
Li, Jian‐Mei
ORCID
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2013-10-15
Volume
170
Issue
5
Pages
1064-1077
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/bph.12336
PMC
PMC3949654
OpenAlex
W1827334661
Cited by
67
References
46
Citations by year
2025: 3 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 6
FWCI
4.40
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Open Research (University of Surrey) (submittedVersion)
  • Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
NADPH oxidase 2, oxidative stress, reactive oxygen species, insulin resistance, endothelial dysfunction, high-fat diet-induced obesity, apocynin, insulin receptor, ERK1/2 activation, eNOS phosphorylation, Akt signaling, acetylcholine-induced vasodilation, metabolic syndrome, hypertension, dyslipidemia
MeSH terms
NADPH Oxidase 2, Age Factors, Animals, Antioxidants, Aorta, Blood Glucose, Blood Pressure, Disease Models, Animal, Dose-Response Relationship, Drug, Endothelium, Vascular, Enzyme Inhibitors, Hypertension, Insulin, Insulin Resistance, Membrane Glycoproteins, Mice, Inbred C57BL, Obesity, Phosphorylation, Receptor, Insulin, Time Factors, Vasodilation, Vasodilator Agents, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, NADPH Oxidases, Mitogen-Activated Protein Kinase 1, Tissue Culture Techniques, Mitogen-Activated Protein Kinase 3, Dyslipidemias, Proto-Oncogene Proteins c-akt, Mice, Nitric Oxide Synthase Type III, Diet, High-Fat

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