AIM: PTX3, an essential component of the humoral arm of innate immunity, increases during the onset of metabolic disorders. Aim of this project was to clarify whether PTX3 behaves as a bystander or actively participates to obesity-related inflammation.

METHODS: PTX3 KO and WT littermates were fed a HFD for 20 weeks. Body weight was measured weekly; fat distribution (magnetic resonance-MRI), glucose tolerance and insulin resistance were checked at 10 and 20 weeks. Histological analysis, immunophenotyping and gene expression of adipose tissues was performed at 20 weeks. Macrophages behavior was studied in vitro.

RESULTS: PTX3 KO mice on HFD gained less weight compared to WT (AUC weight gain WT=190.8±17.4, KO=134.8±10.1), coupled to a decreased accumulation of visceral and subcutaneous fat (p<0.05). In spite of preserved glucose homeostasis, PTX3 deficiency resulted in a reduced infiltration of monocytes and macrophages in the visceral adipose tissue, furthermore, these cells presented a pro-resolving phenotype, as indicated by the reduced expression of CCR2 in monocytes, and increased expression of molecules associated with M2 macrophages (Arg1, YM-1, p<0.01). Gene expression analysis on visceral adipose tissue revealed an enhanced vascularization of this tissue in PTX3 KO mice (increased gene expression of CD31 and VEGF, p<0.05), unbound from VEGF produced by macrophages. Furthermore, the addition of PTX3 to M1 differentiated macrophages induced Il6 upregulation (p<0.05) and a modest M2 markers reduction.

CONCLUSIONS: Our results demonstrate that PTX3 deficiency protects from diet induced-obesity, as a result of a higher vascularization of VAT and M2-macrophages skewing.

03 - PENTRAXIN 3 PLAYS A KEY ROLE IN THE IMMUNOMODULATION OF DIET INDUCED-OBESITY IN MICE