Elizabeth del Ruelas Cinco - Instituto de Investigación en Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y Genómica, C.U.C.S, Universidad de Guadalajara, Guadalajara, Jalisco, México|Programa de Doctorado en Ciencias
Bertha Ruíz Madrigal - Laboratorio de Investigación en Microbiología, Departamento de Microbiología y Patología, C.U.C.S, Universidad de Guadalajara, Guadalajara, Jalisco, México
José Alfredo Dominguez-Rosales - Instituto de Investigación en Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y Genómica, C.U.C.S, Universidad de Guadalajara, Guadalajara, Jalisco, México
Montserrat Maldonado González - Laboratorio de Investigación en Microbiología, Departamento de Microbiología y Patología, C.U.C.S, Universidad de Guadalajara, Guadalajara, Jalisco, México

Objective(s): The present study aimed to evaluate the receptor of advanced glycation end-products (RAGE), NF-kB, NRF2 gene expression, and RAGE cell distribution in peripheral blood mononuclear cells (PBMC) in subjects with obesity and IR compared with healthy subjects.Materials and Methods: The mRNA expression levels of RAGE, NF-kB, NRF2, and GAPDH were determined in PBMC by qPCR in 20 obese (OB), 17 obese with insulin resistance (OB-IR) subjects, and 20 age and sex-matched healthy subjects (HS). RAGE protein expression and its localization were determined by Western Blot and immunocytochemistry (ICC) analysis, total soluble RAGE (sRAGE) and MCP-1 plasma levels by ELISA. Results: RAGE, NF-kB, and NRF2 genes mRNA expression in PBMCs did not show variation between groups. RAGE protein was lower in OB and OB-IR groups; RAGE was located predominantly on the cell-surface in the OB-IR group compared to the HS group (22% vs 9.5%, P<0.001). OB-IR group showed lower sRAGE plasma levels, and correlated negatively with HOMA-IR, ALT parameters (r= -0.374, r= -0.429, respectively), and positively with NFE2L2 mRNA (r= 0.540) PConclusion: In this study, OB-IR subjects did not reflect significant differences in gene expression; however, correlations detected between sRAGE, biochemical parameters, and NRF2, besides the predominant RAGE distribution on the cell membrane in PBMC could be evidence of the early phase of the inflammatory cascade and the subsequent damage in specific tissues in subjects with OB-IR.

AGER protein human, insulin resistance, Obesity, Oxidative stress, Receptor for advanced glycation end products