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Abstract

Introduction: Obesity in childhood is associated with an increased prevalence of diabetes and other traditional cardiometabolic risk factors, suggesting an epidemic of premature cardiovascular disease among today’s youth. Glycotoxins, known as advanced glycationend products (AGE’s), activating via the membrane-bound receptors (mRAGE), have been implicated in the pathophysiology of inflammation, (increased tumor necrosis factor-α [TNF-α ]), insulin resistance and vascular dysfunction in adults, but the role of RAGE in the early stages of metabolic disorders is unknown. In this study, we assessed relationship of cardiometabolicrisk factors, mRNA expression of TNF-α and RAGE in peripheral monocytes in adolescents with obesity.

Methods: Thirty three adolescents,11-16 years of age, with body mass index (BMI) Z-score≥2 were admitted following a 12-hour overnight fast for anthropometrics, lipid profile , fasting peripheral blood sample collection, and a 2-hour 75 gm, oral glucose tolerance test (OGTT). Peripheral blood mononuclear cells (PBMNC) positive for CD14 were isolated from blood. Cells were further analyzed by quantitative PCR for mRNA expression of RAGE and TNF-α. Pearson's coefficients were calculated to assess the associations between RAGE mRNA and cardiometabolicrisk factors as well as TNF-α mRNA levels.

Results: The participants had a mean age of 12.7±1.41 years and BMI-Z score 2.32±0.35 SD with 81 % participants being female; 62 % were Black, 28% Caucasian, 10% were Hispanic. We observed a positive correlation between mRNA levels of RAGE and TNF-α in CD14+ monocytes in blood (r=0.62, p<0.01). However, we did not observe a correlation of BMI, cholesterol or triglyceride with RAGE mRNA levels.

Conclusion: The positive relationship between the monocyte mRNA levels of RAGE and TNF-α suggest involvement of AGE-RAGE axis in obesity-associated inflammation and needs to be further investigated with larger sample size as well as studies in healthy adolescents.

Publication Date

2014

Subject Major(s)

Biology

Keywords

RAGE, obesity, adolescents, cardiometabolic risks, inflammation

Disciplines

Laboratory and Basic Science Research | Other Immunology and Infectious Disease | Translational Medical Research

Current Academic Year

Senior

Faculty Advisor/Mentor

Anshu Gupta MD

Faculty Advisor/Mentor

Daniel Conrad PhD

Rights

© The Author(s)

Receptor of Advanced Glycation Endproducts (RAGE) is Positively Correlated with Tumor Necrosis Factor-α in Adolescents with Obesity

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