title: Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.
abstract: Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.
authors.affiliation: 1EPIUnit - Institute of Public Health,University of Porto,Rua das Taipas, nº 135, 4050-600 Porto,Portugal.
authors.forename: Liane
authors.initials: L
authors.lastname: Correia-Costa
authors.affiliation: 4Department of Pharmacology and Therapeutics, Faculty of Medicine,University of Porto,Rua Dr. Plácido da Costa, 91, Piso 3, 4200-450 Porto,Portugal.
authors.forename: Teresa
authors.identifier: 0000-0001-7230-5020
authors.initials: T
authors.lastname: Sousa
authors.affiliation: 4Department of Pharmacology and Therapeutics, Faculty of Medicine,University of Porto,Rua Dr. Plácido da Costa, 91, Piso 3, 4200-450 Porto,Portugal.
authors.forename: Manuela
authors.identifier: 0000-0002-9509-0613
authors.initials: M
authors.lastname: Morato
authors.affiliation: 1EPIUnit - Institute of Public Health,University of Porto,Rua das Taipas, nº 135, 4050-600 Porto,Portugal.
authors.forename: Dina
authors.initials: D
authors.lastname: Cosme
authors.affiliation: 4Department of Pharmacology and Therapeutics, Faculty of Medicine,University of Porto,Rua Dr. Plácido da Costa, 91, Piso 3, 4200-450 Porto,Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Afonso
authors.affiliation: 3Department of Pediatrics, Faculty of Medicine,University of Porto,Alameda Prof. Hernâni Monteiro, 4200-319 Porto,Portugal.
authors.forename: José C
authors.identifier: 0000-0002-9833-2518
authors.initials: JC
authors.lastname: Areias
authors.affiliation: 8Center for Pediatrics and Adolescent Medicine,Division of Pediatric Nephrology,University of Heidelberg,Im Neuenheimer Feld 430, 69120 Heidelberg,Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
authors.affiliation: 3Department of Pediatrics, Faculty of Medicine,University of Porto,Alameda Prof. Hernâni Monteiro, 4200-319 Porto,Portugal.
authors.forename: António
authors.identifier: 0000-0002-7951-3911
authors.initials: A
authors.lastname: Guerra
authors.affiliation: 1EPIUnit - Institute of Public Health,University of Porto,Rua das Taipas, nº 135, 4050-600 Porto,Portugal.
authors.forename: Alberto C
authors.identifier: 0000-0002-2574-4132
authors.initials: AC
authors.lastname: Afonso
authors.affiliation: 1EPIUnit - Institute of Public Health,University of Porto,Rua das Taipas, nº 135, 4050-600 Porto,Portugal.
authors.forename: Ana
authors.identifier: 0000-0002-7368-9609
authors.initials: A
authors.lastname: Azevedo
authors.affiliation: 4Department of Pharmacology and Therapeutics, Faculty of Medicine,University of Porto,Rua Dr. Plácido da Costa, 91, Piso 3, 4200-450 Porto,Portugal.
authors.forename: António
authors.identifier: 0000-0003-0097-2953
authors.initials: A
authors.lastname: Albino-Teixeira
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000209:etiology*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology*; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide
keywords: ABPM ambulatory blood pressure monitoring; Glomerular filtration rate; HOMA-IR homoeostasis model assessment of insulin resistance; MAP mean arterial pressure; MPO myeloperoxidase; NO nitric oxide; NOS NO synthase; Nitric oxide; Oxidative stress; P-Isop plasma isoprostanes; P-NOx plasma nitrates and nitrites; PWV pulse wave velocity; Paediatric obesity; ROS reactive oxygen species; Risk factors; TAS total antioxidant status; U-H2O2
                  urinary hydrogen peroxide; U-Isop urinary isoprostanes; U-NOx urinary nitrates and nitrites; WHtR waist:height ratio; eGFR estimated glomerular filtration rate; hs-CRP high-sensitivity C-reactive protein