ABSTRACT
Introduction: advanced glycation end-products (AGEs) interact with the receptor for AGEs (RAGE). Full-length RAGE is associated with intracellular signal transduction, and soluble-RAGE (sRAGE) lacks the transmembrane and cytoplasmic domains, acting as a competitive inhibitor ofAGEs-RAGE binding. sRAGE levels in healthy children are associated with cell surface expression of RAGE. However, the expression of RAGE hasnot been explored in childhood obesity.Objective: the study aim was to evaluate the sRAGE levels and the gene expression of RAGE in children and its association with cardiometabolicmarkers.Methods: this is a cross-sectional study with 6-11-year children, 20 with overweight and 20 with obesity. Anthropometric measurements includedwaist circumference (cm) (WC), neck circumference (NC), weight (kg), fat mass (%), trunk fat (kg), muscular mass (kg), height (cm), and bodymass index (BMI) (kg/m2). Blood samples following an overnight fast were collected to measure glucose (mg/dl) and lipid profile with colorimetricmethods. sRAGE was determined in serum using the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription (RT-qPCR)was performed to analyze RAGE transcripts in peripheral blood mononuclear cells isolated by Ficoll®-Hypaque.Results: we found higher RAGE (p = 0.0315) and lower sRAGE (p = 0.0305) levels in the obesity group. sRAGE level showed a negative correlation with RAGE (r = -0.35) and BMI (r = -0.24), and positive with HDL-cholesterol (r = 0.29). Regression analysis suggests that HDL-C andRAGE levels are predictors of sRAGE levels.Conclusions: expression of RAGE is associated with lower sRAGE levels in childhood obesity. Moreover, obese children show higher cardiometabolic risk markers, and a positively associated with sRAGE. (AU)
Introducción: los productos finales de glicación avanzada (AGE) interactúan con el receptor de AGE (RAGE). El RAGE de longitud completaestá asociado con la transducción de señales intracelulares y el RAGE soluble (sRAGE) carece de los dominios transmembrana y citoplásmico,actuando como un inhibidor competitivo de la unión de AGE-RAGE. Los niveles de sRAGE en niños sanos están asociados con la expresión deRAGE en la superficie celular. Sin embargo, la expresión de RAGE no se ha explorado en la obesidad infantil.Objetivo: el objetivo del estudio fue evaluar los niveles de sRAGE y la expresión génica de RAGE en niños y su asociación con marcadorescardiometabólicos.Métodos: se trata de un estudio transversal con niños de seis a once años, 20 con sobrepeso y 20 con obesidad. Las medidas antropométricasincluyeron la circunferencia de la cintura (cm) (CC), la circunferencia del cuello (NC), el peso (kg), la masa grasa (%), la grasa del tronco (kg),la masa muscular (kg), la altura (cm) y el índice de masa corporal (IMC) (kg/m2). Se tomaron muestras de sangre después de una noche deayuno para medir glucosa (mg/dl) y el perfil de lípidos con métodos colorimétricos. Los sRAGE se determinaron en suero utilizando un ensayoinmunoabsorbente ligado a enzimas (ELISA). Se realizó una transcripción inversa cuantitativa (RT-qPCR) para analizar los transcritos de RAGE encélulas mononucleares de sangre periférica aisladas por Ficoll®-Hypaque.Resultados: encontramos niveles más altos de RAGE (p = 0,0315) y más bajos de sRAGE (p = 0,0305) en el grupo de obesidad. El nivel de sRAGE mostró una correlación negativa con RAGE (r = -0,35) e IMC (r = -0,24), y positiva con el colesterol HDL (r = 0,29). El análisis de regresión sugiere que los niveles de HDL-C y RAGE predicen los niveles de sRAGE.Conclusiones: la expresión de RAGE se asocia con niveles más bajos de sRAGE en la obesidad infantil. ... (AU)
Subject(s)
Humans , Child , Adolescent , Pediatric Obesity/diagnosis , Overweight , Biomarkers , Cross-Sectional StudiesABSTRACT
Introduction: Introduction: advanced glycation end-products (AGEs) interact with the receptor for AGEs (RAGE). Full-length RAGE is associated with intracellular signal transduction, and soluble-RAGE (sRAGE) lacks the transmembrane and cytoplasmic domains, acting as a competitive inhibitor of AGEs-RAGE binding. sRAGE levels in healthy children are associated with cell surface expression of RAGE. However, the expression of RAGE has not been explored in childhood obesity. Objective: the study aim was to evaluate the sRAGE levels and the gene expression of RAGE in children and its association with cardiometabolic markers. Methods: this is a cross-sectional study with 6-11-year children, 20 with overweight and 20 with obesity. Anthropometric measurements included waist circumference (cm) (WC), neck circumference (NC), weight (kg), fat mass (%), trunk fat (kg), muscular mass (kg), height (cm), and body mass index (BMI) (kg/m2). Blood samples following an overnight fast were collected to measure glucose (mg/dl) and lipid profile with colorimetric methods. sRAGE was determined in serum using the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription (RT-qPCR) was performed to analyze RAGE transcripts in peripheral blood mononuclear cells isolated by Ficoll®-Hypaque. Results: we found higher RAGE (p = 0.0315) and lower sRAGE (p = 0.0305) levels in the obesity group. sRAGE level showed a negative correlation with RAGE (r = -0.35) and BMI (r = -0.24), and positive with HDL-cholesterol (r = 0.29). Regression analysis suggests that HDL-C and RAGE levels are predictors of sRAGE levels. Conclusions: expression of RAGE is associated with lower sRAGE levels in childhood obesity. Moreover, obese children show higher cardiometabolic risk markers, and a positively associated with sRAGE.
Introducción: Introducción: los productos finales de glicación avanzada (AGE) interactúan con el receptor de AGE (RAGE). El RAGE de longitud completa está asociado con la transducción de señales intracelulares y el RAGE soluble (sRAGE) carece de los dominios transmembrana y citoplásmico, actuando como un inhibidor competitivo de la unión de AGE-RAGE. Los niveles de sRAGE en niños sanos están asociados con la expresión de RAGE en la superficie celular. Sin embargo, la expresión de RAGE no se ha explorado en la obesidad infantil. Objetivo: el objetivo del estudio fue evaluar los niveles de sRAGE y la expresión génica de RAGE en niños y su asociación con marcadores cardiometabólicos. Métodos: se trata de un estudio transversal con niños de seis a once años, 20 con sobrepeso y 20 con obesidad. Las medidas antropométricas incluyeron la circunferencia de la cintura (cm) (CC), la circunferencia del cuello (NC), el peso (kg), la masa grasa (%), la grasa del tronco (kg), la masa muscular (kg), la altura (cm) y el índice de masa corporal (IMC) (kg/m2). Se tomaron muestras de sangre después de una noche de ayuno para medir glucosa (mg/dl) y el perfil de lípidos con métodos colorimétricos. Los sRAGE se determinaron en suero utilizando un ensayo inmunoabsorbente ligado a enzimas (ELISA). Se realizó una transcripción inversa cuantitativa (RT-qPCR) para analizar los transcritos de RAGE en células mononucleares de sangre periférica aisladas por Ficoll®-Hypaque. Resultados: encontramos niveles más altos de RAGE (p = 0,0315) y más bajos de sRAGE (p = 0,0305) en el grupo de obesidad. El nivel de sRAGE mostró una correlación negativa con RAGE (r = -0,35) e IMC (r = -0,24), y positiva con el colesterol HDL (r = 0,29). El análisis de regresión sugiere que los niveles de HDL-C y RAGE predicen los niveles de sRAGE. Conclusiones: la expresión de RAGE se asocia con niveles más bajos de sRAGE en la obesidad infantil. Además, los niños obesos muestran marcadores de riesgo cardiometabólico más elevados y una asociación positiva con sRAGE.
ABSTRACT
RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant, proposed as an inhibitor of RAGE activity. -374 T/A and -429 T/C polymorphisms of the advanced glycation end products receptor AGER gene are associated with the development of some diseases, such as type of cancer, cardiovascular disease, and micro and macrovascular disease in diabetes among others but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy men without MS, and 80 men with MS according to the harmonized criteria. -374 T/A and -429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between Non-MS and MS groups (-374 T/A p = 0.48, p = 0.57 and -429 T/C p = 0.36, p = 0.59). Significant differences were found in fasting glucose levels and diastolic blood pressure among the genotypes of the -374 T/A polymorphism in the Non-MS group (p < 0.01 and p = 0.008). Glucose levels were different between -429 T/C genotypes in the MS group (p = 0.02). sRAGE levels were similar in both groups, but in the Non-MS group showed a significant difference between individuals with only 1 or 2 components of the metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for -374 T/A; recessive model p = 0.48, dominant model p = 0.42 for -429 T/C). -374 T/A and -429 T/C polymorphisms are not associated with MS in Mexican population and have no influence on serum sRAGE levels.
ABSTRACT
Obesity can lead children and adolescents to an increased cardiovascular disease (CVD) risk. A diet supplemented with Plantago psyllium has been shown to be effective in reducing LDL-C and IL-6 in adolescents. However, there are no studies that have explored small-dense LDL (sdLDL) or HDL subclasses. The aim of this study was to evaluate the impact of a fiber dietary intervention on LDL and HDL subclasses in adolescents with obesity. In this parallel, double blind, randomized clinical trial, the participants were assigned to Plantago psyllium or placebo (10g/day for 7 weeks). We randomized 113 participants, and evaluated and analyzed 100 adolescents (50 in each group), 15 to 19 years with a body mass index of 29-34. We measured biochemical markers LDL and HDL subclasses using the Lipoprint system (Quantimetrix) and IL-6 by ELISA. Post-treatment there was a decrease in sdLDL between the groups 2.0 (0-5.0) vs 1 (0-3.0) mg/dl (p = 0.004), IL-6 median 3.32 (1.24-5.96) vs 1.76 (0.54-3.28) pg/ml, p <0.0001. There were no differences in HDL subclasses and no adverse effects were reported in either group.Conclusions: Small dense LDL and IL-6 reduced in adolescents with obesity when consuming Plantago psyllium. This may be an early good strategy for the reduction of cardiovascular disease risk in this vulnerable population.Trial registration: ISRCTN # 14180431. Date assigned 24/08/2020 What is Known: ⢠Supplementing the diet with Plantago psyllium lowers LDL-C levels. What is New: ⢠First evidence that soluble fiber supplementation like Plantago psyllium decreases small dense LDL particles in association with lowered IL-6, reducing the risk of cardiovascular disease in obese adolescents.
Subject(s)
Plantago , Psyllium , Adolescent , Child , Double-Blind Method , Humans , Interleukin-6 , ObesityABSTRACT
Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.
Subject(s)
Gene Expression Regulation , Metabolic Syndrome/complications , Metabolic Syndrome/metabolism , Neoplasms/complications , Neoplasms/metabolism , Receptor for Advanced Glycation End Products/metabolism , Adiponectin/metabolism , Adipose Tissue/metabolism , Animals , Disease Progression , Humans , Hyperglycemia/metabolism , Hypertension/metabolism , Inflammation , Insulin-Like Growth Factor I/metabolism , Leptin/metabolism , Ligands , Mice , Obesity/metabolism , Peroxisome Proliferator-Activated Receptors/metabolism , Rats , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism , Wnt Proteins/metabolismABSTRACT
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 (Iß). 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 Iß (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 Iß (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 Iß, so it could be suggested as a biochemical marker of impaired endothelial function.
Subject(s)
Pediatric Obesity/blood , Receptor for Advanced Glycation End Products/blood , Vascular Diseases/blood , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Lysine/analogs & derivatives , Lysine/blood , Male , Triglycerides/blood , Vascular Stiffness , Young AdultABSTRACT
Nε-carboxymethyl-lysine (CML) is measured in food, but there is a controversy concerning the most convenient yet reliable method(s) for this task. This work compares three different ELISA assays and HPLC-ESI-ITMS/MS for the analysis of CML in several food items. The four methods showed the same decreasing order of CML concentration: beef, bacon>chicken > fish>dairy products>grain products>fruits/vegetables. HPLC-ESI-ITMS/MS results highly correlated with those obtained by ELISA performed with monoclonal CML-antibody (ß=0.98, p<0.0001) whereas My Bio Source® kit results were not correlated with those provided by Lamider®. Small differences of CML concentrations in food items prepared by different culinary treatment were clearly distinguished by HPLC-ESI-ITMS/MS, but could not always be detected by ELISA. This work demonstrates a reasonable relationship between CM determined by ELISA and HPLC-ESI-ITMS/MS and therefore supports the implementation of ELISA in food CML/AGEs screening.
Subject(s)
Chromatography, High Pressure Liquid/methods , Enzyme-Linked Immunosorbent Assay/methods , Fruit/chemistry , Glycation End Products, Advanced/analysis , Lysine/analogs & derivatives , Mass Spectrometry/methods , Meat/analysis , Vegetables/chemistry , Animals , Cattle , Fishes , Food Contamination/analysis , Lysine/analysis , SwineABSTRACT
PURPOSE OF REVIEW: This report analyzes emerging evidence about the role of dietary advanced glycation end products (AGEs) as a cardiometabolic risk factor. Two important aspects are discussed: First, the modulation of AGE load by dietary AGEs; second, if the evidence of clinical and observational studies is enough to make dietary recommendations towards lowering AGE intake. RECENT FINDINGS: Clinical studies in subjects with diabetes mellitus have shown that high intake of dietary AGEs increases inflammation markers, oxidative stress, and could impair endothelial function. In subjects at risk for cardiometabolic diseases (with overweight, obesity, or prediabetes), dietary AGE restriction decreases some inflammatory molecules and improves insulin sensitivity. However, studies in healthy subjects are limited, and not all of the studies have shown a decrease in circulating AGEs. Therefore, it is still unclear if dietary AGEs represent a health concern for people potentially at risk for cardiometabolic diseases. The evidence shows that dietary AGEs are bioavailable and absorbed, and the rate of excretion depends on dietary intake. The metabolic fate of most dietary AGEs remains unknown. Regardless, most studies have shown that by diminishing AGE intake, circulating levels will also decrease. Thus, dietary AGEs can modulate the AGE load at least in patients with DM, overweight, or obesity. Studies with specific clinical outcomes and large-scale observational studies are needed for a better risk assessment of dietary AGEs and to establish dietary recommendations accordingly.
Subject(s)
Cardiovascular Diseases/complications , Diet , Glycation End Products, Advanced/adverse effects , Metabolic Syndrome/complications , Diabetes Mellitus/pathology , Glycation End Products, Advanced/chemistry , Humans , Receptor for Advanced Glycation End Products/metabolism , Risk FactorsABSTRACT
Three α-ketoaldehydes, potentially present in high fructose agave syrups (HFASs) as intermediates of the Maillard reaction, were determined. A previously reported HPLC-FLD procedure based on pre-column derivatisation with 4-methoxy-o-phenylenediamine was adopted, yielding the method quantification limits 0.11 mg/kg, 0.10mg/kg, 0.09 mg/kg for glyoxal, methylglyoxal (MGo) and diacetyl, respectively. The obtained results revealed high concentrations of methylglyoxal in HFASs (average 102 ± 91 mg/kg, range 15.6-315 mg/kg) as compared to commercial Mexican bee honeys or corn syrups. Hydrogen peroxide was generated in all HFASs upon dilution, yet to less extent than in bee honeys. HFASs presented bacteriostatic activity against Bacillus subtilis and Escherichia coli; catalase addition had minimum effect on the assay results in syrups with elevated MGo. Principal component analysis revealed direct association between growth inhibition and MGo. It is concluded that elevated concentration of MGo in HFASs is at least in part responsible for their non-peroxide bacteriostatic activity.
Subject(s)
Agave/chemistry , Chromatography, High Pressure Liquid/methods , Fructose/chemistry , Honey/analysis , Animals , BeesABSTRACT
In this work, the effect of cadmium (0-5.0 mg L(-1) as cadmium chloride, Cd(II)) and selenium (0-2.0 mg L(-1) as sodium selenite, Se(IV)) was studied in Lepidium sativum with specific focus on glyoxal (GO) and methylglyoxal (MGO) and on the cellular distribution of both elements under different exposure conditions. The concentrations of two reactive α-ketoaldehydes present as natural metabolites and as by-products of lipid peroxidation, were increased in plants treated with Cd(II), providng complementary experimental evidence on element phytotoxicity in garden cress, in terms of oxidative damage. Even though for higher than 1.0 mg L(-1) Se in medium similar adverse effect was found, under simultaneous exposure to both elements the changes in GO and MGO concentrations were clearly attenuated as compared to a single stressor treatment. This effect was accompanied by lower uptake of the two elements, significant decrease of their relative distribution in the fraction containing polar compounds and their increase in fraction corresponding to insoluble cell fragments/components, suggesting that the direct in vivo interaction between two element forms might be involved in the favorable effects of simultaneous treatment with Cd(II) + Se(IV). The fluorescence spectra obtained for biomass extracts corresponding to different exposure conditions suggested possible in vivo formation of CdSe quantum dots; however further studies are needed for ultimate identification and characterization of such nanoparticulate species.
