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

Frontiers in Immunology

Immunology

Alessandro dos Santos Farias¹  Fernando O. Martinez²  Silvio Roberto Consonni³  Bianca G. Castelucci³  Izadora L. A. Rabelo⁴  Claudiana Lameu⁴  Daniel White⁵  Martin Brunel Whyte⁶  Barbara A. Fielding⁷  Daniela Carlos⁸  Jefferson Elias-Oliveira⁸  Marco Aurélio Ramirez Vinolo⁹  Laís P. Pral⁹  Wislei Riuper Osório^1,10  Hosana Gomes Rodrigues^1,11  Roberta Nicolli Sagiorato^1,11  Beatriz Burger^1,11  Thamiris Candreva^1,11  Mariana R. Pacheco^1,11  Jéssica Rondoni Silva^1,11  Helena L. Fisk^1,12  Philip C. Calder^1,13 

[1] Autoimmune Research Lab, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil;Department of Biochemical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom;Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil;Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil;Department of General Surgery, The Royal Surrey National Health Service (NHS) Foundation Trust Hospital, Guildford, United Kingdom;Department of Medicine, King’s College Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom;Department of Clinical & Experimental Medicine, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom;Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom;Departments of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil;Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil;Laboratory of Manufacturing Advanced Materials, School of Applied Sciences, University of Campinas, Limeira, Brazil;Laboratory of Nutrients and Tissue Repair, School of Applied Sciences, University of Campinas, Limeira, Brazil;School of Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;School of Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;National Institute for Health and Care Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton National Health Service (NHS) Foundation Trust and University of Southampton, Southampton, United Kingdom;

关键词: tissue repair;    diabetes;    chronic wounds;    nutrition;    inflammation;    fatty acids;   

DOI  :  10.3389/fimmu.2023.1141731

 received in 2023-01-10, accepted in 2023-05-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
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