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

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.

Acute effects of fatty acids on autophagy in NPY neurones.

High-fat diet (HFD) feeding is deleterious to hypothalamic tissue, leading to inflammation and lipotoxicity, as well as contributing to central insulin resistance. Autophagy is a process that restores cellular homeostasis by degrading malfunctioning organelles and proteins. Chronic HFD-feeding down-regulates hypothalamic autophagy. However, the effects of short-term HFD-feeding and the saturated fatty acid palmitate (PA) on hypothalamic autophagy and in neurones that express neuropeptide Y (NPY) and agouti-related peptide remains unknown. Therefore, we assessed hypothalamic autophagy after 1 and 3 days of HFD-feeding. We also injected PA i.c.v and analysed the modulation of autophagy in hypothalamic tissue. Both interventions resulted in changes in autophagy-related gene profiles without significant differences in protein content of p62 and LC3B-II, markers of the autophagy pathway. When we assessed native NPY neurones in brain slices from PA-treated animals, we observed increased levels of Atg7 and LC3B protein in response to PA treatment, indicating the induction of autophagy. We then tested the direct effects of fatty acids using the immortalised hypothalamic NPY-expressing neuronal cell model mHypoE-46. We found that PA, but not palmitoleate (PO) (a monounsaturated fatty acid), was able to induce autophagy. Co-treatment with PA and PO was able to block the PA-mediated induction of autophagy, as assessed by flow cytometry. When the de novo ceramide synthesis pathway was blocked with myriocin pre-treatment, we observed a decrease in PA-mediated induction of autophagy, although there was no change with the toll-like receptor 4 inhibitor, TAK-242. Taken together, these findings provide evidence that saturated and unsaturated fatty acids can differentially regulate hypothalamic autophagy and that ceramide synthesis may be an important mediator of those effects. Understanding the mechanisms by which dietary fats affect autophagy in neurones involved in the control of energy homeostasis will provide potential new pathways for targeting and containing the obesity epidemic.

Production of vegetable oil blends and structured lipids and their effect on wound healing / Produção de misturas de óleos vegetais e lípidos estruturados e o seu efeito na cicatrização de feridas

Two oil blends (sunflower/canola oils 85/15 (BL1) and canola/linseed oils 70/30 (BL2)), were prepared and enzymatically interesterified to be applied to surgically-induced wounds in rats. Following surgery, the animals were submitted to the Treatment with Physiological Saline (TPS) (control group), Blends (TBL), and Structured Lipids (TSL). The control group (TPS) received physiological saline solution for 15 days. In TBL, BL1 was administered during the inflammation phase (days 0-3) and BL2 in the tissue formation and remodeling phase (days 4-15). In TSL, Structured Lipid 1 (SL1) and Structured Lipid 2 (SL2) were used instead of BL1 and BL2, respectively. The aim of this study was to compare wound closure evolution among rats treated with the blends or structured lipids versus control rats treated with physiological saline. The wound healing process was evaluated by measuring the wound areas along the treatments and the concentrations of cytokines. An increase in the areas of wounds treated with the blends and structured lipids in the inflammatory phase was observed, followed by a steeper closure curve compared to wounds treated with physiological saline. The changes observed during the inflammatory phase suggest a potential therapeutic application in cutaneous wound healing which should be further investigated...

Duas misturas de óleos vegetais (girassol/canola 85/15 (BL1) e canola/linhaça, 70/30 (BL2) foram preparadas e interesterificadas por via enzimática para serem aplicadas em feridas induzidas cirurgicamente em ratos. Após a cirurgia, os animais foram submetidos ao tratamento com soro fisiológico (TPS) (grupo controle), tratamento com as misturas (TBL) e tratamento com os lipídios estruturados (TSL). O grupo controle (TPS) recebeu soro fisiológico por 15 dias. Em TBL, BL1 foi administrada durante a fase de inflamação (dias 0-3) e BL2 na fase de formação de tecido e remodelação (dias 4-15). Em TSL, os lipídios estruturados SL1 e SL2 foram usados em vez de BL1 e BL2, respectivamente. O objetivo deste estudo foi avaliar a evolução do fechamento das feridas dos grupos de ratos tratados com as misturas ou lipídios estruturados em comparação com os ratos do grupo controle, tratados com soro fisiológico. O processo de cicatrização das feridas foi avaliado através da medição das áreas das feridas ao longo dos tratamentos e pela determinação das concentrações de citocinas. Observou-se aumento das áreas das feridas tratadas com as misturas e os lipídios estruturados na fase inflamatória, seguida por um fechamento acentuado de feridas comparado com o tratamento com solução salina. As mudanças observadas durante a fase inflamatória sugerem uma potencial aplicação terapêutica na cicatrização de feridas cutâneas, fazendo-se necessárias investigações posteriores...

Comparative effects of DHA and EPA on cell function.

Fish oil supplementation has been reported to be generally beneficial in autoimmune, inflammatory and cardiovascular disorders. Most researchers have attributed these beneficial effects to the high content of omega-3 fatty acids in fish oil (FO). The effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are not differentiated in most studies. In fact, up to 1990, purified DHA was not available for human use and there was no study regarding its effects on human immune response. In this review, the differences in the effects of these two fatty acids on cell function are discussed. Studies have shown that EPA and DHA have also different effects on leukocyte functions such as phagocytosis, chemotactic response and cytokine production. DHA and EPA modulate differently expression of genes in lymphocytes. Activation of intracellular signaling pathways involved with lymphocyte proliferation is also differently affected by these two fatty acids. In relation to insulin producing cell line RINm5F, DHA and EPA are cytotoxic at different concentrations and the proteins involved with cell death are differently modulated by these two fatty acids. Substantial improvement in the therapeutic usage of omega-3 fatty acid-rich FO will be possible with the discovery of the different mechanisms of actions of DHA and EPA.