Association of chemokines IP-10/CXCL10 and I-TAC/CXCL11 with insulin resistance and enhance leukocyte endothelial arrest in obesity.

Autores de INCLIVA

• Luisa Maria Hueso Soler

  Autor

• Rebeca Ortega Herraiz

  Autor

• Esther Benito Casado

  Autor

• 

  Sergio Martinez Hervas

  Autor

• Marta Peiró Signes

  Autor

• Miguel Civera Andres

  Autor

• 

  Maria Jesus Sanz Ferrando

  Autor

• 

  Laura Piqueras Ruiz

  Autor

• 

  Jose Tomas Real Collado

  Autor

Participantes ajenos a INCLIVA

• Moreno, Beatriz

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Inflamación

  

  Leading Researcher

  Maria Jesus Sanz Ferrando

• Grupo de Investigación en Receptores Nucleares en Patología Cardiometabólicas

  

  Established Researcher

  Laura Piqueras Ruiz

• Grupo de Investigación sobre Riesgo Cardiometabólico y Diabetes

  

  Leading Researcher

  Sergio Martinez Hervas

Abstract

BACKGROUND AND AIMS: Obesity is a key contributing factor to incidental type 2 diabetes and cardiovascular disease. CXCR3 receptor and its ligands CXCL 10 and 11 are associated with atherosclerosis and cardiovascular disease. The aim of our study was to analyse the role of the CXCR3 ligands on insulin resistance (IR) and endothelial dysfunction in human obesity. METHODS AND RESULTS: We have studied 45 obese patients (mean age 44 ± 6 years, body mass index 45 ± 9 kg/m(2)) who were selected for Roux-Y-gastric bypass surgery and 21 non obese control subjects with similar age and gender distribution. We measured by ELISA the circulating levels of the CXCR3 ligands interferon-? inducible protein 10 (IP-10/CXCL10) and interferon-?-inducible T-cell alpha chemoattractant (I-TAC/CXCL11). Using an ex vivo procedure with the flow chamber assay, we have investigated the effect of such chemokines on endothelial leukocytes arrest under dynamic conditions. Peripheral blood levels of CXCL10 and CXCL11 were significantly higher in obese subjects than in controls (p < 0.001) and significantly correlated with BMI, waist circunference and HOMA-IR. Obese patients with HOMA-IR index above 75th percentile showed highest increase of circulating CXCL10 and CXCL11 values. Under dynamic flow conditions, the enhanced adhesion of patient leukocytes to TNFa-induced human arterial endothelial cells was partly dependent on CXCR3. CONCLUSIONS: The study demonstrates that CXCL10 and CXCL11 are associated with IR and enhance leukocyte endothelial arrest in obese subjects. Blockade of CXCR3 signaling might be a new therapeutic approach for the prevention of obesity-associated cardiovascular co-morbidities.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords

• CXCL10; CXCL11; CXCR3; Chemokines; Endothelial dysfunction; Insulin resistance; Leukocyte adhesion; Obesity