Obesity is characterized by excessive expansion of adipose tissue (AT), accompanied by a constant basal immune response that does not resolve adequately, known as low-grade chronic inflammation. There is evidence that subcutaneous AT is a weaker vascular and metabolic risk factor, but visceral AT shows altered inflammatory and angiogenic responses associated with increased metabolic dysfunction in obese subjects. However, the immune mediators involved in the different responses are not precisely known. Based on preliminary data, our initial hypothesis is that the dysregulation of the CCR9-CCL25 and CXCR3-CCL10/CCL11 chemokine axes contributes to AF dysfunction in obesity and the development of insulin resistance and diabetes. The objectives of this proposal are: i) to evaluate the circulating levels and expression of CCR9-CCL25 in AT of patients with morbid obesity, ii) their association with metabolic parameters linked to AT dysfunction and insulin resistance, and iii) to investigate ex vivo the effects of CCR9 blockade on inflammation in AT. On the other hand, based on recent published studies where we observed higher levels of CXCL10 and CXCL11 in obese subjects, and their association with an increase in insulin resistance and AT dysfunction, our next objective is v) to investigate the possible therapeutic effects of pharmacological blockade of the CXCR3 axis in an animal model of obesity. Therefore, the main objective of this project is to explore new inflammatory and angiogenic markers that could be involved in metabolic dysfunction in obesity through the use of different experimental approaches in patients with morbid obesity and animal models of obesity.

Description of the datasetDetermination of CCL25 levels in obese morbid patients.Study of leukocyte-endothelial cells interactions in obese patientEffects of CXCR3 blockade in an animal model of obesity