Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice.

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.

• Authors: Beatriz Burger, Roberta Nicolli Sagiorato, Jéssica Rondoni Silva, Thamiris Candreva, Mariana R Pacheco, Daniel White, Bianca G Castelucci, Laís P Pral, Helena L Fisk, Izadora L A Rabelo, Jefferson Elias-Oliveira, Wislei Riuper Osório, Silvio Roberto Consonni, Alessandro Dos Santos Farias, Marco Aurélio Ramirez Vinolo, Claudiana Lameu, Daniela Carlos, Barbara A Fielding, Martin Brunel Whyte, Fernando O Martinez, Philip C Calder, Hosana Gomes Rodrigues
• Journal: Frontiers in immunology (Front Immunol) Vol. 14 Pg. 1141731 ( 2023) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 37359536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Burger, Sagiorato, Silva, Candreva, Pacheco, White, Castelucci, Pral, Fisk, Rabelo, Elias-Oliveira, Osório, Consonni, Farias, Vinolo, Lameu, Carlos, Fielding, Whyte, Martinez, Calder and Rodrigues.

Chemical References

• Eicosapentaenoic Acid
• Interleukin-10
• PPAR gamma
• Fatty Acids, Omega-3
• Collagen

Topics

• Animals
• Mice
• Eicosapentaenoic Acid (pharmacology)
• Interleukin-10 (pharmacology)
• PPAR gamma
• Diabetes Mellitus, Experimental
• Diabetes Mellitus, Type 1 (drug therapy)
• Fatty Acids, Omega-3
• Wound Healing
• Collagen (metabolism)
• Dietary Supplements