Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammation Resolution and Angiogenesis in Fat Grafts in a Controlled Mouse Model.

Abstract

Background: 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 on postoperative inflammation and graft survival in vivo.

Methods: Fish oil (or saline for the control group) was administered intragastrically 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 after transplantation. Serum C-reactive protein concentration was determined by enzyme-linked immunosorbent assay. Gene expression levels of inflammatory factors, perilipin-1, and vascular endothelial growth factor in the grafts were analyzed by quantitative real-time polymerase chain reaction. Hematoxylin and eosin, Masson trichrome, immunohistochemistry, and immunofluorescence staining were performed.

Results: Omega-3 PUFAs reduced the serum C-reactive protein concentration. In addition, in the grafts of the fish oil group, expression of proinflammatory factors was reduced, and expression of anti-inflammatory factors was increased. CD11b+ immunofluorescence intensity at days 14 and 30 was reduced, and 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 immunohistochemical control staining (CD11b, F4/80, and CD206). Gene expression of vascular endothelial growth factor at day 14 and perilipin-1 at days 30 and 90 were increased. Perilipin-1+ percentage area and CD31+ percentage area at day 90 were increased. Inflammatory cell infiltration and fibrosis were decreased.

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

Clinical relevance statement: The authors' findings suggest the effectiveness of using inflammatory resolution mechanisms to promote fat graft survival and provide a fundamental support for clinical use of omega-3 PUFAs in autologous fat transplantation.