D-lactate and Low Molecular AGEs Are Elevated in Obese Adolescents: Evidence for Carbonyl Stress in Adolescent Obesity

Glycation and carbonyl stress produced by methylglyoxal (MG) as a consequence of triose flux in glycolysis has been implicated in the etiology of metabolic syndrome and diabetes complications. An integrated estimation of MG flux is provided by measuring concentrations of its catabolite D-lactate in serum. However, no studies have explored the pathway in childhood obesity. Objective: Study serum concentrations of D-lactate and low molecular weight advanced glycation end-products (LMWAGE) in lean vs adolescents with obesity. Material and Methods: We conducted a cross-sectional study of 30 lean and 30 obese adolescents between the ages of 15-19 years. D-lactate was measured kinetically in serum ultrafiltrates by an adaptation of a colorimetric method from Sigma. Total and LMW-AGEs were measured by fluorescence (Excitation: λ 370 nm, Emission: λ 440 nm). The Ethical Committee of the Institution approved this study and informed consent was obtained from the participant adolescents and their parents. Results: The obesity group showed significantly (* p \u3c 0.01, ** p \u3c 0.001) higher levels of: % body fat 35.0 ± 9**, systolic BP 116.0 ± 8.1 mmHg** and diastolic BP, 72.9 ± 7.1*mmHg, waist 96.1 ± 11.6 cm** and hip circumferences 110.2 ± 8 cm**, HbA1c 5.1 ± 0.6*. D-lactate was 4.5 +/- 2.5 nmol/l in controls vs 7.4 +/- 4.2 vs. nmol/l in obese subjects **. LMW/total AGE were 0.48 (0.44-052) AU in controls vs 0.61 (0.55-0.67) AU in obese subjects**. Conclusions: D-lactate levels and LMW-AGEs are higher (64% and 27% respectively) in adolescents with obesity as compared to lean controls. Our data is compatible with the presence of an increased production of MG associated with protein modification that results in LMW-AGE (partial proteolysis of AGE proteins) increases in serum. This increased carbonyl stress may be of etiological significance. Sources of Research Support: Project supported by DAIP Universidad de Guanajuato (project 011/2015) and Touro Universit

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

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, mass-spectrometry 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.info:eu-repo/semantics/acceptedVersio

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

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=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-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.Supported by Centro para el Desarrollo Tecnológico e Industrial, Spain, Project reference: IPT-20111008, and Generalitat de Catalunya grants 2017SGR1719 and 2017SGR696. MJ is a "Serra Hunter" program fellow. Supported by Instituto de Salud Carlos III, Spain, Project reference: 17-00134, co-financed by FEDER Funds A way to make Europe