No abstract

Objective: The aim of this study was to evaluate soluble receptor for advanced glycation end products (sRAGE) and advanced glycation end products (AGEs) in adolescents with and without obesity (OB) and their correlation with vascular damage. Methods: This is a cross-sectional study with 15–19 years old adolescents: 33 with OB and 33 with normal weight (NW), each group included 17 male and 16 female. Lipid profile, insulin, carboxymethylysine (CML), sRAGE, total AGEs, and dietary AGEs intake (dAGEs) were evaluated. Vascular damage was measured by flow-mediated vasodilation (FMD) and arterial stiffness index (Iβ). Homeostatic model assessment-insulin (HOMA-IR) and atherogenic index (AI) were calculated. Results: The group with OB had higher triglycerides (TG; p < 0.0001), AI (p < 0.001), HOMA-IR (p < 0.0001), dAGEs intake (p < 0.0001), lower CML (p = 0.05), total AGEs (p < 0.01), sRAGE (p < 0.001), and FMD (p < 0.002). In the total group, sRAGE correlated with AI (r = –0.26 p = 0.037); in the NW group, CML correlated with Iβ (r = –0.36; p = 0.037); and in the group of adolescents with OB, sRAGE correlated with FMD (r = –0.37; p = 0.037) and Iβ (r = 0.47; p = 0.006), while CML and total AGEs correlated with AI, p = 0.007 and p < 0.01, respectively). Conclusions: The group of adolescents with OB showed higher cardiometabolic risk as shown by higher TG, AI, HOMA-IR, and lower sRAGE and FMD. sRAGE correlated negatively with FMD and positively with Iβ, so it could be suggested as a biochemical marker of impaired endothelial function.

Obese adolescents display subclinical signs of IR and endothelial dysfunction. Higher serum sd-LDL levels correlated positively with D-lactate levels. These findings suggest an association between atherogenic dyslipoproteinemia and whole body MG fluxes already detectable in apparently healthy obese adolescents.

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days-old) Duroc breed females (n=20) either with a standard growth diet (3800 KCal/day) or one with a high-calorie content (5200 KCal/day) during 70 days. Computerized tomography, massspectrometry based metabolomics, and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia, in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride, and sterol classes) were also linked with obesity-traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.