Effects of omega-3 polyunsaturated fatty acids on inflammation resolution and angiogenesis in fat grafts in a controlled mouse model.

Abstract

Background: The upregulation or delay of acute inflammation at any stage limits fat graft survival. Active endogenous inflammation resolution mechanisms and mediators are novel therapeutic tools for inflammation. This study explored the effects of supplementation of omega-3 polyunsaturated fatty acids (PUFAs) deriving specialized proresolving mediators (SPMs) on postoperative inflammation and graft survival in vivo.

Methods: Fish oil (FO) (or saline for the control group) was intragastrically administered in the C57BL/6N mouse fat graft model for a week before and after transplantation. The mice were euthanized at 3, 7, 14, 30, or 90 days posttransplantation. Serum C-reactive protein (CRP) concentration was determined via enzyme-linked immunosorbent assay (ELISA); gene expression levels of inflammatory factors, perilipin-1 and vascular endothelial growth factor (VEGF) in the grafts were analyzed via quantitative real-time PCR (QPCR); hematoxylin and eosin (H&E), masson's trichrome, immunohistochemistry (IHC) and immunofluorescence (IF) staining were performed.

Results: Omega-3 PUFAs reduced the serum CRP concentration. Additionally, in the grafts of FO group, proinflammatory factors expression was reduced while anti-inflammatory factors expression was increased; the CD11b+ IF intensity at Days 14 and 30 was reduced, the F4/80+/CD11b+ ratio at Days 3 and 7 and the CD206+/F4/80+ ratio at Days 7, 14, and 30 were increased, consistent with the results of IHC control staining (CD11b, F4/80 and CD206); the gene expression of VEGF at Day 14 and perilipin-1 at Days 30 and 90 were increased; the perilipin-1+ %area and CD31+ %area at Day 90 were increased; inflammatory cell infiltration and fibrosis were decreased.

Conclusion: Omega-3 PUFAs can enhance inflammation resolution and angiogenesis and promotes fat graft survival in a controlled mouse model.