PAFR in adipose tissue macrophages is associated with anti-inflammatory phenotype and metabolic homeostasis

Metabolic dysfunction is associated with adipose tissue inflammation and macrophage infiltration. The Platelet Activating Factor Receptor (PAFR) is expressed in several cell types and binds to PAF and oxidized phospholipids. Engagement of PAFR in macrophages drives them towards the anti-inflammatory phenotype. In the present study, we investigated whether genetic deficiency of PAFR affects the phenotype of adipose tissue macrophages (ATM) and its effect on glucose and insulin metabolism. PAFR-deficient (PAFRKO) and wild type mice (WT) were fed standard (SD) or high fat diet (HFD). Glucose and insulin tolerance tests were performed by blood monitoring. ATM were evaluated by FACS for phenotypic markers. Gene and protein expression was investigated by real-time PCR and western-blot, respectively. Results showed that the epididymal adipose tissue of PAFRKO mice had increased gene expression of Ccr7, Nos2, Il6, and Il12, associated topro-inflammatory mediators, and reduced expression of the anti-inflammatory IL10 . Moreover, the adipose tissue of PAFRKO presented higher pro-inflammatory macrophages, characterized by an increased frequency of F4/80+CD11c+ cells. Blood monocytes of PAFRKO mice also exhibited a pro-inflammatory phenotype (increased frequency of Lys6C+.cells) and PAFR-ligands were detected in the serum of both PAFRKO and WT. Regarding metabolic parameters, compared to WT, PAFRKO mice had: i) higher weight gain andserum glucose concentration levels; ii) decreased in...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research