Upregulation of angiostatic chemokines CXCL10 and CXCL11 in morbid obese patients and their implication in adipose tissue angiogenesis

抄録

Background. The increasing incidence and prevalence of obesity is a global health issue. In obesity, inadequate adipose tissue vascularization has been associated with vascular rarefaction, leukocyte chemotaxis and inflammation, thus contributing to the transition to metabolic dysfunction. However, the underlying mechanisms that regulates angiogenesis in adipose tissue are still largely unknown. In the present study, we investigated the role of the chemokine receptor CXCR3 and its chemokine ligands CXCL10 and CXCL11 on adipose tissue angiogenesis in morbid obese patients.

Methods. The study group comprised 50 morbid obese patients with a mean age of 44 years undergoing laparoscopic Roux Y gastric bypass surgery. We measured circulating levels of CXCL10 and CXCL11, and their expression in paired subcutaneous and visceral adipose tissue samples. Additionally, we evaluated ex vivo the functional role of the CXCR3 axis on capillary growth in AT explants from morbid obese patients.

Results. Plasma CXCL10 and CXCL11 levels were significantly higher in morbid obese patients than in controls, and correlated positively with body mass index. Furthermore, in morbid obese patients, visceral adipose tissue exhibited blunted angiogenic growth when compared with subcutaneous adipose tissue, which was associated with a marked upregulation of CXCL10 and CXCL11 expression. Interestingly, blockade of CXCR3 with a neutralizing antibody significantly increased capillary sprouting in visceral fat deposits from morbid obese patients.

Conclusions. Our findings suggest that pharmacological blockade of CXCR3 could represent a novel therapy to prevent adipose tissue dysfunction in obesity. This study was supported by grants, CPII13 00025, PI15 00082 and PIE15 00013 from the Carlos III Health Institute, the Spanish Ministry of Economy and Competiveness, and the European Regional Development Fund