AUTHOR=Burger Beatriz , Sagiorato Roberta Nicolli , Silva Jéssica Rondoni , Candreva Thamiris , Pacheco Mariana R. , White Daniel , Castelucci Bianca G. , Pral Laís P. , Fisk Helena L. , Rabelo Izadora L. A. , Elias-Oliveira Jefferson , Osório Wislei Riuper , Consonni Silvio Roberto , Farias Alessandro dos Santos , Vinolo Marco Aurélio Ramirez , Lameu Claudiana , Carlos Daniela , Fielding Barbara A. , Whyte Martin Brunel , Martinez Fernando O. , Calder Philip C. , Rodrigues Hosana Gomes TITLE=Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1141731 DOI=10.3389/fimmu.2023.1141731 ISSN=1664-3224 ABSTRACT=

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro. In vivo, topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells.