Plasma resistin levels are associated with homocysteine, endothelial activation, and nitrosative stress in obese youths.

OBJECTIVE: To evaluate whether serum resistin levels are related to cardiovascular risk in obese children. DESIGN AND METHODS: Cross-sectional study of 110 children (40 normal weight and 70 severely obese). Clinical and biochemical parameters, including lipid profile, fasting glucose and insulin, and homocysteine, were determined. The levels of adipokines (adiponectin, leptin, and resistin), markers of inflammation (high-sensitivity C-reactive protein (hs-CRP)), endothelial activation (serum concentrations of soluble intercellular and vascular cellular adhesion molecule-1 (sICAM-1, sVCAM-1)), and oxidative/nitrosative stress (malondialdehyde and urinary nitrate/nitrite) were measured. RESULTS: A partial correlation adjusted by gender, Tanner stage, and body mass index in obese children showed that resistin was significantly related to central obesity (p<0.002), insulin resistance (p<0.005), and homocysteine (p<0.001). No association was found with other metabolic risk factors or hs-CRP levels. Malondialdehyde (p<0.043) and sVCAM-1 (p<0.002) were positively correlated whereas urinary nitrate/nitrite was negatively correlated (p<0.007). In multiple regression analysis homocysteine, sVCAM-1, and urinary nitrate/nitrite remained independent determinants of resistin levels (R(2) adjusted=0.347, p=0.000). CONCLUSIONS: Resistin could be considered as a promising marker for future cardiovascular disease in obese children.

Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children.

OBJECTIVE: To examine vitamin D, parathyroid hormone, and serum calcium-phosphorus levels relationships to biomarkers of oxidative/nitrosative stress, inflammation, and endothelial activation, potential contributors for vascular complications in obese children. STUDY DESIGN: Cross-sectional clinical study of 66 obese Caucasian children aged 7 to 14 years. Cardiovascular risk factors were assessed. Malondialdehyde and myeloperoxidase as measures of oxidative stress, and plasma nitrite+nitrate, urinary nitrate, and 3-nitrotyrosine as markers of nitrosative stress were measured. Adipocytokines, inflammatory molecules (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α), endothelial activation molecules (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule 1 [sVCAM-1]), E-selectin, and vascular endothelial growth factor were also investigated. Serum 25-hydroxy-cholecalciferol [25(OH)D], intact parathormone, and calcium-phosphorus levels were determined in these children and in a comparison group of 39 non-obese children. RESULTS: Obese children had a significantly lower 25(OH)D level (P = .002) and a higher intact parathormone (P = .011) than non-obese children. Phosphorus and the calcium-phosphorus product were also significantly higher (P < .0001). Insufficient serum concentrations of 25(OH)D (<20 ng/mL) were detected in 5% of normal children and in 30% of the obese children. In the obese children with vitamin D insufficiency, malondialdehyde, myeloperoxidase, 3-nitrotyrosine, interleukin-6, and sVCAM-1 were substantially elevated. A partial correlation analysis showed an inverse relationship of 25(OH)D levels with 3-nitrotyrosine (r = -0.424, P = .001), and sVCAM-1 (r = -0.272, P = .032). CONCLUSIONS: Insufficient 25(OH)D levels were detected in severely obese children with increased markers of oxidative/nitrosative stress, inflammation, and endothelial activation.

Polyamines are increased in obese children and are related to markers of oxidative/nitrosative stress and angiogenesis.

CONTEXT: Polyamines (putrescine, spermidine, and spermine) are polycationic amines derived from arginine, which is the precursor of nitric oxide (NO). Due to the close relationship between the metabolism of polyamines and NO metabolism, the alteration in polyamine homeostasis can affect the NO bioavailability at the endothelium. OBJECTIVES: The objective of the study was to test the hypothesis that childhood obesity is associated with a significant modification of blood polyamines and to investigate the presence of correlation between these molecules, circulating markers of oxidative and nitrosative stress, and endothelial dysfunction. DESIGN AND SETTING: This was an observational analytical case-control study conducted at one tertiary care center. PATIENTS AND METHODS: The study was performed with 102 children aged 7-14 yr (60 obese, 42 nonobese). Blood polyamines were measured by HPLC. Metabolites of the NO pathway, oxidative stress parameters, inflammatory markers, adhesion molecules, and adipocytokines were also determined. RESULTS: Polyamine levels were significantly higher in obese children. Among them, spermine was the polyamine with the more discriminatory power, taking into account the obesity. In all children, spermine levels were related to biomarkers of oxidative/nitrosative stress, inflammation, and leptin and to adhesion molecules, soluble E-selectin, and soluble intercellular adhesion molecule-1. Only in obese children was there a positive correlation with vascular endothelial growth factor and a negative correlation with 3'-nitrotyrosine levels. CONCLUSIONS: Polyamine levels are increased in childhood obesity and correlated to markers of oxidative/nitrosative stress and angiogenesis. This finding implicates polyamine metabolism in the complications of obesity. Their potential utility as a clinical tool remains to be elucidated.

Nitric oxide production is increased in severely obese children and related to markers of oxidative stress and inflammation.

OBJECTIVE: Nitric oxide (NO) is the major endothelium-derived relaxing factor. The aim of the present study was to evaluate NO synthesis and metabolism in severely obese children with different degrees of metabolic risk and to ascertain their relation with the parameters of oxidative stress and inflammation. METHODS: The study involved 60 obese children evaluated with respect to metabolic risk factors (MRFs) (32<4 MRFs and 28 ≥ 4 MRFs) and 50 normal weight children between 7 and 14 years of age. Nutritional status was assessed by clinical and anthropometric examination. MRFs (serum lipid profile, insulin resistance indexes, blood pressure) in addition to uric acid, homocysteine, leptin, and inflammatory markers were measured. Plasma nitrite, nitrate and nitrotyrosine concentrations, and urinary nitrate were determined as markers of NO production and nitrosative stress. Malondialdehyde, 8-isoprostane F(2α), and advanced oxidation protein products were analyzed in plasma to assess oxidative stress. RESULTS: Compared with healthy controls, the obese children had significantly increased concentrations of markers of NO synthesis and nitrosative and oxidative stress that were correlated with each another. Increased NO production in obese children was associated with MRFs; plasma nitrate to waist circumference (r=0.388, p=0.003), uric acid (r=0.404, p<0.001), and tumor necrosis factor α (r=0.302, p=0.021), and plasma nitrite to triglycerides (r=0.432, p<0.001). CONCLUSION: NO synthesis and nitrosative stress are increased in severely obese children and correlated with anthropometric parameters indicative of abdominal obesity, oxidative stress and inflammatory markers.