Postprandial inflammation and metabolic dysfunction in adolescents with obesity and insulin resistance

Abstract

BackgroundPostprandial dyslipidemia is an independent risk factor for cardiovascular disease, and inflammatory and metabolic markers are implicated in its pathogenesis. We hypothesize that the postprandial inflammatory and metabolic profiles of adolescents with obesity and insulin resistance (IR) is dysregulated and more informative to the pathogenesis of postprandial dyslipidemia than at fasting. MethodsAdolescents with normal weight (N=15) and with obesity (N=30) were recruited in Toronto, ON, and underwent a six-hour oral fat tolerance test. Eight cytokines were assessed using an automated sandwich immunoassay, and a metabolomics profile (>133 metabolites) was quantified using liquid chromatography tandem mass spectrometry and nuclear magnetic resonance spectroscopy. A lipid/lipoprotein, bile acid, and anthropometric profile were previously quantified in this cohort. ResultsAmong the studied cytokines, levels of interleukin (IL)-6 were significantly elevated in obesity throughout the entire postprandial response (p<0.05). Numerous metabolites, namely acylcarnitines, biogenic amines, and glycerophospholipids were significantly downregulated postprandially, whereas amino acids were predominantly elevated, in obesity compared to NW. Correlational analyses revealed strong (-0.5> Spearman rho > 0.5) and significant (p<0.05) associations between tumour necrosis factor- α, IL-6, and IL-8 and an atherogenic lipid/lipoprotein phenotype, and adiposity and IR, while IL-1β, IL-18, monokine induced by interferon-γ, and IL-10 were strongly associated with bile acid species in the postprandial state. Conclusion Adolescents with obesity and IR exhibit significant fasting and postprandial dysregulation of several inflammatory and metabolic markers integral to lipid metabolism. These data may offer novel subclinical biomarkers for early metabolic and cardiovascular diseases, such as postprandial dyslipidemia, in at-risk adolescents.