AUTHOR=Corica Domenico , Aversa Tommaso , Ruggeri Rosaria Maddalena , Cristani Mariateresa , Alibrandi Angela , Pepe Giorgia , De Luca Filippo , Wasniewska Malgorzata 

TITLE=Could AGE/RAGE-Related Oxidative Homeostasis Dysregulation Enhance Susceptibility to Pathogenesis of Cardio-Metabolic Complications in Childhood Obesity?

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00426

DOI=10.3389/fendo.2019.00426

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> Advanced glycation end-products (AGEs) and their cell receptor (RAGE) are involved in the pathophysiology of cardio-metabolic diseases. Interaction of AGEs with RAGE results in increased generation of oxygen radicals and pro-inflammatory cytokines. Circulating soluble RAGE (sRAGE) interacts with AGEs in order to counterbalance the negative effects of AGEs-RAGE interaction.</p><p><bold>Objectives:</bold> To define factors influencing AGEs, sRAGE, AGEs/sRAGE-ratio, and advanced oxidation-protein products (AOPPs) levels and to investigate changes in oxidative balance among overweight/obese children.</p><p><bold>Materials and methods:</bold> Cross-sectional, one Center, case-control study included 41 overweight and obese children aged between 5 and 16 years and 36 lean matched controls. Inclusion criteria were: BMI ≥ 1 SD; term birth; no genetic or endocrine causes of obesity; no associated chronic diseases neither chronic therapies. All patients underwent clinical and biochemical investigations (lipid and glucose profiles, liver, renal and thyroid function tests, uric acid, C-reactive protein (CRP), AGEs, sRAGE, and AOPPs serum concentrations). Significance was established at 0.050.</p><p><bold>Results:</bold> AOPPs, AGEs/sRAGE-ratio, HOMA-IR, triglycerides, triglycerides/HDL-ratio, total cholesterol (TC)/HDL-ratio, atherogenic-index of plasma (AIP), uric acid, CRP were significantly higher, whereas sRAGE and HDL were significantly lower in overweight/obese children than controls. sRAGE was significantly negatively correlated with BMI SD, TC/HDL-ratio, CRP, AOPPs, and positively with HDL. AGE/sRAGE-ratio and AOPPs were significantly positively correlated with BMI SD, TC/HDL-ratio, AIP, CRP, and negatively with HDL. BMI SD was independently associated with AGEs/sRAGE-ratio (<italic>B</italic> = 0.06; <italic>p</italic> = 0.008), AOPPs (<italic>B</italic> = 0.13; <italic>p</italic> = 0.02), and sRAGE (<italic>B</italic> = −73.18; <italic>p</italic> = 0.000).</p><p><bold>Conclusions:</bold> We demonstrated, for the first time in a pediatric cohort, a significant higher value of AGEs/sRAGE-ratio among overweight/obese children, expression of a relative shift to oxidant from anti-oxidant factors, suggesting an AGE/RAGE-related oxidative homeostasis dysregulation that could enhance susceptibility to oxidative/inflammatory tissues damage. Severity of overweight, influencing the increase of oxidative stress in human organism and even in children, may contribute to the pathogenesis of long-term cardiovascular and metabolic alterations.</p>