THE ROLE OF CXCL17 IN A MOUSE MODEL OF DIET-INDUCED OBESITY

CXCL17 is a mucosal chemokine that attracts dendritic cells and monocytes to specific tissues. CXCL17 is mainly expressed in the gastrointestinal tract and has been shown to have anti-inflammatory effects. Its recently described receptor, CXCR8, is a G-protein-coupled receptor involved in metabolic function. Therefore, we decided to study the role of CXCL17 and CXCR8 in obesity, in which the effect of anti-inflammatory macrophages is essential to maintain tissue homeostasis. To conduct this study, we used a mouse model of diet-induced obesity to compare Cxcl17^-/- mice and wild type (WT) C57BL/6 mice. The mice were fed either a 10% or 60% fat diet for four months. They were weighed weekly and a glucose tolerance test was performed after two months. Plasma samples were used to perform an adipokine assay to detect levels of obesity-related cytokines and hormones. After four months, gastrointestinal tract tissue was isolated and isolated RNA was used to measure expression levels of CXCL17 and obesity-associated hormones by qPCR. Our data show that Cxcl17^-/- mice fed a high fat diet gained more weight than WT mice. In addition, CXCL17 is highly expressed in the upper gastrointestinal tract in WT mice under homeostatic conditions. Obese Cxcl17^-/- mice exhibited impaired glucose tolerance. Adipokine assay results revealed differences in obesity-associated molecules between WT and Cxcl17^-/- mice. These results indicate that CXCL17 influences the development of obesity and systemic metabolic dysfunction. Therefore, we conclude that the CXCL17/CXCR8 axis represents a novel pathway that regulates metabolic responses.