ArticleBritish journal of pharmacology2013
Crucial roles of Nox2-derived oxidative stress in deteriorating the function of insulin receptors and endothelium in dietary obesity of middle-aged mice.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 67 citations in OpenAlex.
- Association between the oxidative balance score and all-cause and cardiovascular mortality in patients with cardiovascular-kidney-metabolic syndrome--a retrospective cohort study from the NHANES.BMC cardiovascular disorders · 2025Article
- LDL-c/HDL-c Ratio and NADPH-Oxidase-2-Derived Oxidative Stress as Main Determinants of Microvascular Endothelial Function in Morbidly Obese Subjects.Antioxidants (Basel, Switzerland) · 2024Article
- NOX2 deficiency exacerbates diet-induced obesity and impairs molecular training adaptations in skeletal muscle.Redox biology · 2023Article
- Cross-Talk of NADPH Oxidases and Inflammation in Obesity.Antioxidants (Basel, Switzerland) · 2023Review
- Endothelial Extracellular Signal-Regulated Kinase/Thromboxane A2/Prostanoid Receptor Pathway Aggravates Endothelial Dysfunction and Insulin Resistance in a Mouse Model of Metabolic Syndrome.Journal of the American Heart Association · 2022Article
- The non-linear relationship between triglyceride-glucose index and risk of chronic kidney disease in hypertensive patients with abnormal glucose metabolism: A cohort study.Frontiers in medicine · 2022Article
- p47Antioxidants (Basel, Switzerland) · 2021Article
- Integrative proteomic network analyses support depot-specific roles for leucine rich repeat LGI family member 3 in adipose tissues.Experimental and therapeutic medicine · 2021Article
- Adipocyte-Endothelium Crosstalk in Obesity.Frontiers in endocrinology · 2021Review
- AqueousJournal of diabetes and metabolic disorders · 2020Article
- In vivo and in silico characterization of apocynin in reducing organ oxidative stress: A pharmacokinetic and pharmacodynamic study.Pharmacology research & perspectives · 2020Article
- NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity.Antioxidants (Basel, Switzerland) · 2020Article
- Deficiency of T-type voltage-gated calcium channels results in attenuated weight gain and improved endothelium-dependent dilatation of resistance vessels induced by a high-fat diet in mice.Journal of physiology and biochemistry · 2020Article
- Differential contribution of Nox1, Nox2 and Nox4 to kidney vascular oxidative stress and endothelial dysfunction in obesity.Redox biology · 2020Article
- CD73Journal of extracellular vesicles · 2020Article
- Astragaloside IV promotes the eNOS/NO/cGMP pathway and improves left ventricular diastolic function in rats with metabolic syndrome.The Journal of international medical research · 2020Article
- The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism.Antioxidants & redox signaling · 2019Review
- The Role of NADPH Oxidases in the Etiology of Obesity and Metabolic Syndrome: Contribution of Individual Isoforms and Cell Biology.Antioxidants & redox signaling · 2019Review
- Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?International journal of molecular sciences · 2019Review
- Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature.The Journal of clinical investigation · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
background and purposeSystemic 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 Nox2, 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 Nox2 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
resultsCompared to NCD WT mice, HFD WT mice developed obesity, insulin resistance, dyslipidaemia and hypertension. Aortic vessels from these mice showed significantly increased Nox2 expression and ROS production, accompanied by significantly increased ERK1/2 activation, reduced insulin receptor expression, decreased Akt 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 Nox2 KO mice given the same HFD. CONCLUSIONS AND IMPLICATIONS: In conclusion, Nox2-derived ROS played a key role in damaging insulin receptor and endothelial function in dietary obesity after middle-age. Targeting Nox2 could represent a valuable therapeutic strategy in the metabolic syndrome.
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