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.

Anthocyanins ameliorate obesity-associated metainflammation: Preclinical and clinical evidence.

The growing rates of obesity worldwide call for intervention strategies to help control the pathophysiological consequences of weight gain. The use of natural foods and bioactive compounds has been suggested as such a strategy because of their recognized antioxidant and anti-inflammatory properties. For example, polyphenols, especially anthocyanins, are candidates for managing obesity and its related metabolic disorders. Obesity is well known for the presence of metainflammation, which has been labeled as an inflammatory activation that leads to a variety of metabolic disorders, usually related to increased oxidative stress. Considering this, anthocyanins may be promising natural compounds able to modulate several intracellular mechanisms, mitigating oxidative stress and metainflammation. A wide variety of foods and extracts rich in anthocyanins have become the focus of research in the field of obesity. Here, we bring together the current knowledge regarding the use of anthocyanins as an intervention tested in vitro, in vivo, and in clinical trials to modulate metainflammation. Most recent research applies a wide variety of extracts and natural sources of anthocyanins, in diverse experimental models, which represents a limitation of the research field. However, the literature is sufficiently consistent to establish that the in-depth molecular analysis of gut microbiota, insulin signaling, TLR4-triggered inflammation, and oxidative stress pathways reveals their modulation by anthocyanins. These targets are interconnected at the cellular level and interact with one another, leading to obesity-associated metainflammation. Thus, the positive findings with anthocyanins observed in preclinical models might directly relate to the positive outcomes in clinical studies. In summary and based on the entirety of the relevant literature, anthocyanins can mitigate obesity-related perturbations in gut microbiota, insulin resistance, oxidative stress and inflammation and therefore may contribute as a therapeutic tool in people living with obesity.

The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes.

Macrophages and lymphocytes demonstrate metabolic plasticity, which is dependent partly on their state of activation and partly on the availability of various energy yielding and biosynthetic substrates (fatty acids, glucose, and amino acids). These substrates are essential to fuel-based metabolic reprogramming that supports optimal immune function, including the inflammatory response. In this review, we will focus on metabolism in macrophages and lymphocytes and discuss the role of fatty acids in governing the phenotype, activation, and functional status of these important cells. We summarize the current understanding of the pathways of fatty acid metabolism and related mechanisms of action and also explore possible new perspectives in this exciting area of research.

Anti-inflammatory effects of oleic acid and the anthocyanin keracyanin alone and in combination: effects on monocyte and macrophage responses and the NF-κB pathway.

Monocyte recruitment and activation of macrophages are essential for homeostasis but are also related to the development and progression of cardiometabolic diseases. The management of inflammation with dietary components has been widely investigated. Two components that may influence inflammation are unsaturated fatty acids such as oleic acid (OA; 18:1cis-9) and antioxidant compounds like anthocyanins. Molecular and metabolic effects of such bioactive compounds are usually investigated in isolation, whereas they may be present in combination in foods or the diet. Considering this, we aimed to analyze the effects of OA and the anthocyanin keracyanin (AC) alone and in combination on toll-like receptor-mediated inflammatory responses in monocytes and macrophages. For this, THP-1-derived macrophages and monocytes were exposed to 3 treatments: OA, AC, or the combination (OAAC) and then stimulated with lipopolysaccharide. Inflammation-related gene expression and protein concentrations of IL-1ß, TNF-α, IL-6, MCP-1, and IL-10 were assessed. Also, NFκBp65, IκBα, and PPAR-γ protein expression were determined. OA, AC, and OAAC decreased pNFκBp65, PPARγ, IκBα, TNF-α, IL-1ß, IL-6, and MCP-1 and increased IL-10. MCP-1 protein expression was lower with OAAC than with either OA and AC alone. Compared to control, OAAC decreased mRNA for TLR4, IκKα, IκBα, NFκB1, MCP-1, TNF-α, IL-6, and IL-1ß more than OA or AC did alone. Also, IL-10 mRNA was increased by OAAC compared with control, OA, and AC. In summary, OA and AC have anti-inflammatory effects individually but their combination (OAAC) exerts a greater effect.

Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial.

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.

Is There an Advantage in Enriching Parenteral Lipid Emulsions Containing Fatty Acids From Fish Oil With Medium-Chain Triglycerides? A Study on Body Pool Concentrations of ω-3 Fatty Acids in Lewis Rats.

BACKGROUND: The addition of medium-chain triglycerides (MCTs) into parenteral lipid emulsions rich in fatty acids from fish oil (FOLEs) has been shown to improve their clearance and extrahepatic uptake. We assessed whether this effect could favor the leukocyte uptake of ω-3 polyunsaturated fatty acids (PUFAs) for immunomodulatory purposes METHODS: Following 5-day adaptation in metabolic cages, 42 male Lewis rats fed with AIN-93M chow were killed (baseline control group [BC]) or submitted to central venous catheterization and distributed into (1) surgical control group without parenteral infusion (chow group), (2) test emulsion (MCT/LCT/FO) group with the parenteral infusion of a FOLE containing 40% MCT, and (3) control emulsion group (LCT/FO) with the parenteral infusion of an FOLE without MCT. The 2 FOLEs had similar ω-3 PUFA contents and ω-6/ω-3 PUFA ratios and were infused during 48 and 72 hours. Concentrations of ω-3 and ω-6 PUFAs in plasma, liver, and blood mononuclear and polymorphonuclear leukocytes were assessed by gas chromatography RESULTS: In both FOLE groups, leukocyte concentrations of ω-3 PUFAs peaked after 48 hours' infusion (vs BC). At this time point, plasma concentrations of ω-3 PUFAs were higher in MCT/LCT/FO group than in LCT/FO group and the opposite was found in the liver (P<.05), but no differences in PUFA concentrations were observed between these groups in leukocytes (P>.05) CONCLUSION: The ω-3 PUFAs provided by FOLEs rich in MCT were less incorporated by liver and remained more available for extrahepatic cell delivery, but this did not result in a clear benefit in increasing their incorporation by peripheral leukocytes.

Palmitoleic acid reduces high fat diet-induced liver inflammation by promoting PPAR-γ-independent M2a polarization of myeloid cells.

Palmitoleic acid (POA, 16:1n-7) is a lipokine that has potential nutraceutical use to treat non-alcoholic fatty liver disease. We tested the effects of POA supplementation (daily oral gavage, 300 mg/Kg, 15 days) on murine liver inflammation induced by a high fat diet (HFD, 59% fat, 12 weeks). In HFD-fed mice, POA supplementation reduced serum insulin and improved insulin tolerance compared with oleic acid (OA, 300 mg/Kg). The livers of POA-treated mice exhibited less steatosis and inflammation than those of OA-treated mice with lower inflammatory cytokine levels and reduced toll-like receptor 4 protein content. The anti-inflammatory effects of POA in the liver were accompanied by a reduction in liver macrophages (LM, CD11c+; F4/80+; CD86+), an effect that could be triggered by peroxisome proliferator activated receptor (PPAR)-γ, a lipogenic transcription factor upregulated in livers of POA-treated mice. We also used HFD-fed mice with selective deletion of PPAR-γ in myeloid cells (PPAR-γ KOLyzCre+) to test whether the beneficial anti-inflammatory effects of POA are dependent on macrophages PPAR-γ. POA-mediated improvement of insulin tolerance was tightly dependent on myeloid PPAR-γ, while POA anti-inflammatory actions including the reduction in liver inflammatory cytokines were preserved in mice bearing myeloid cells deficient in PPAR-γ. This overlapped with increased CD206+ (M2a) cells and downregulation of CD86+ and CD11c+ liver macrophages. Moreover, POA supplementation increased hepatic AMPK activity and decreased expression of the fatty acid binding scavenger receptor, CD36. We conclude that POA controls liver inflammation triggered by fat accumulation through induction of M2a macrophages independently of myeloid cell PPAR-γ.

Response to Bistrian BR. Parenteral Fish-Oil Emulsions in Critically Ill COVID-19 Emulsions.

In this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish-oil emulsions in critically ill patients with Coronavirus Disease 2019 (COVID-19). We consider that immune-modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish-oil emulsions, may be important to change the course of COVID-19's death pathway. Prescriptions should be based on body weight (eg, 0.2-g pure fish-oil lipid emulsion/kg body weight/d) and also should consider combining the parenteral administration of fish-oil emulsions with low oral aspirin intake to trigger resolvin synthesis from EPA and DHA.

Docosahexaenoic acid slows inflammation resolution and impairs the quality of healed skin tissue.

There is no consensus on the effects of omega-3 (ω-3) fatty acids (FA) on cutaneous repair. To solve this problem, we used 2 different approaches: (1) FAT-1 transgenic mice, capable of producing endogenous ω-3 FA; (2) wild-type (WT) mice orally supplemented with DHA-enriched fish oil. FAT-1 mice had higher systemic (serum) and local (skin tissue) ω-3 FA levels, mainly docosahexaenoic acid (DHA), in comparison with WT mice. FAT-1 mice had increased myeloperoxidase (MPO) activity and content of CXCL-1 and CXCL-2, and reduced IL-10 in the skin wound tissue three days after the wound induction. Inflammation was maintained by an elevated TNF-α concentration and presence of inflammatory cells and edema. Neutrophils and macrophages, isolated from FAT-1 mice, also produced increased TNF-α and reduced IL-10 levels. In these mice, the wound closure was delayed, with a wound area 6-fold bigger in relation with WT group, on the last day of analysis (14 days post-wounding). This was associated with poor orientation of collagen fibers and structural aspects in repaired tissue. Similarly, DHA group had a delay during late inflammatory phase. This group had increased TNF-α content and CD45+F4/80+ cells at the third day after skin wounding and increased concentrations of important metabolites derived from ω-3, like 18-HEPE, and reduced concentrations of those from ω-6 FA. In conclusion, elevated DHA content, achieved in both FAT-1 and DHA groups, slowed inflammation resolution and impaired the quality of healed skin tissue.

Eighteen­carbon trans fatty acids and inflammation in the context of atherosclerosis.

Endothelial dysfunction is a pro-inflammatory state characterized by chronic activation of the endothelium, which leads to atherosclerosis and cardiovascular disease (CVD). Intake of trans fatty acids (TFAs) is associated with an increased risk of CVD. This risk is usually associated with industrial TFAs (iTFAs) rather than ruminant TFAs (rTFAs); however it is not clear how specific TFA isomers differ in their biological activity and mechanisms of action with regard to inflammation. Here we review the literature on 18­carbon TFAs, including the research associating their intake or levels with CVD and studies relating 18­carbon TFA exposure to modulation of inflammatory processes. The evidence associating iTFAs with CVD risk factors is fairly consistent and studies in humans usually show a relation between iTFAs and higher levels of inflammatory markers. In contrast, studies in humans, animals and in vitro suggest that rTFAs have null or mildly beneficial effects in cardiovascular health, metabolic parameters and inflammatory markers, although the evidence is not always consistent. More studies are needed to better identify the beneficial and detrimental effects of the different TFAs, including those with 18 carbons.

Oral administration of EPA-rich oil impairs collagen reorganization due to elevated production of IL-10 during skin wound healing in mice.

Wound healing is an essential process for organism survival. Some fatty acids have been described as modulators of wound healing. However, the role of omega-3 fatty acids is unclear. In the present work, we investigate the effects of oral administration of eicosapentaenoic acid (EPA)-rich oil on wound healing in mice. After 4 weeks of EPA-rich oil supplementation (2 g/kg of body weight), mice had increased serum concentrations of EPA (20:5ω-3) (6-fold) and docosahexaenoic acid (DHA; 22:6ω-3) (33%) in relation to control mice. Omega-3 fatty acids were also incorporated into skin in the EPA fed mice. The wound healing process was delayed at the 3rd and 7th days after wounding in mice that received EPA-rich oil when compared to control mice but there was no effect on the total time required for wound closure. Collagen reorganization, that impacts the quality of the wound tissue, was impaired after EPA-rich oil supplementation. These effects were associated with an increase of M2 macrophages (twice in relation to control animals) and interleukin-10 (IL-10) concentrations in tissue in the initial stages of wound healing. In the absence of IL-10 (IL-10-/- mice), wound closure and organization of collagen were normalized even when EPA was fed, supporting that the deleterious effects of EPA-rich oil supplementation were due to the excessive production of IL-10. In conclusion, oral administration of EPA-rich oil impairs the quality of wound healing without affecting the wound closure time likely due to an elevation of the anti-inflammatory cytokine IL-10.

Palmitoleic Acid has Stronger Anti-Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids.

SCOPE: Fatty acids (FAs) may affect endothelial cell (EC) function, influencing atherogenesis and inflammatory processes. Palmitoleic acid (POA) has been described as an anti-inflammatory FA. However, its effects on ECs are underexplored. This study compares the effects of POA with those of palmitic acid (PA) and oleic acid (OA) on EC inflammatory responses. METHODS AND RESULTS: EAHy926 cells (EC lineage) are exposed to PA, OA, or POA, and stimulated with tumor necrosis factor (TNF)-α. Associated with the FA's own incorporation, PA induces a twofold increase in arachidonic acid, while POA increases the amount of cis-vaccenic acid. PA, but not OA, enhances the production of IL-6 and IL-8 in response to TNF-α. In contrast, POA decreases production of monocyte chemotactic protein (MCP)-1, IL-6, and IL-8 compared to PA. TNF-α increases surface intercellular adhesion molecule-1 expression previously decreased by POA. TNF-α stimulation increases the expression of NFκB, cyclooxygenase (COX)-2, MCP-1, and IL-6 genes and reduces the expression of peroxisome proliferator-activated receptor (PPAR)-α gene. PA enhances the expression of MCP-1, IL-6, and COX-2 genes, while POA downregulates these genes, decreases expression of NFκB, and upregulates PPAR-α gene expression. CONCLUSION: POA has anti-inflammatory effects on ECs stimulated with TNF-α and may counter endothelial dysfunction.

Immunomodulatory role of branched-chain amino acids.

Branched-chain amino acids (BCAAs) have been associated with immunomodulation since the mid-1970s and 1980s and have been used in the nutritional therapy of critically ill patients. Evidence shows that BCAAs can directly contribute to immune cell function, aiding recovery of an impaired immune system, as well as improving the nutritional status in cancer and liver diseases. Branched-chain amino acids may also play a role in treatment of patients with sepsis or trauma, contributing to improved clinical outcomes and survival. Branched-chain amino acids, especially leucine, are activators of the mammalian target of rapamycin (mTOR), which, in turn, interacts with several signaling pathways involved in biological mechanisms of insulin action, protein synthesis, mitochondrial biogenesis, inflammation, and lipid metabolism. Although many in vitro and human and animal model studies have provided evidence for the biological activity of BCAAs, findings have been conflicting, and the mechanisms of action of these amino acids are still poorly understood. This review addresses several aspects related to BCAAs, including their transport, oxidation, and mechanisms of action, as well as their role in nutritional therapy and immunomodulation.

Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids.

Obesity leads to an inflammatory condition that is directly involved in the etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types of cancer. The classic inflammatory response is an acute reaction to infections or to tissue injuries, and it tends to move towards resolution and homeostasis. However, the inflammatory process that was observed in individuals affected by obesity and metabolic syndrome differs from the classical inflammatory response in certain respects. This inflammatory process manifests itself systemically and it is characterized by a chronic low-intensity reaction. The toll-like receptor 4 (TLR4) signaling pathway is acknowledged as one of the main triggers of the obesity-induced inflammatory response. The aim of the present review is to describe the role that is played by the TLR4 signaling pathway in the inflammatory response and its modulation by saturated and omega-3 polyunsaturated fatty acids. Studies indicate that saturated fatty acids can induce inflammation by activating the TLR4 signaling pathway. Conversely, omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti-inflammatory actions through the attenuation of the activation of the TLR4 signaling pathway by either lipopolysaccharides or saturated fatty acids.

High Dose of A Conjugated Linoleic Acid Mixture Increases Insulin Resistance in Rats Fed Either A Low Fat or A High Fat Diet.

Obesity and related diseases are becoming more prevalent. Conjugated linoleic acid (CLA) might be a useful coadjutant treatment helping to decrease fat mass. However, the precise impact of CLA is unclear because the decreased body fat mass is followed by an increase in insulin resistance. This study aimed to evaluate some of the consequences of a high dose of CLA in rats fed a normal low fat or a high fat diet for 30 days. Male Wistar rats were separated into 4 groups (each n = 10): Control group receiving 7% fat (soybean oil); CLA group receiving 4% soybean oil and 3% CLA mixture; animal fat (AF) group, receiving 45% fat (lard); and animal fat plus CLA (AF+CLA) group, receiving 42% lard and 3% CLA mixture. The CLA mixture contained 39.32 mole% c9,t11-CLA and 40.50 mole% t10,c12-CLA. After 30 days, both CLA groups (CLA and AF+CLA groups) developed insulin resistance, with an increase in glucose in the fasting state and in an insulin tolerance test. The CLA group had increased liver weight and percentage of saturated fatty acids in liver and adipose tissue. Feeding the high fat diet resulted in increased hepatic triacylglycerol accumulation and this was exacerbated by dietary CLA. It is concluded that a high dose of CLA mixture increases insulin resistance and exacerbates hepatic steatosis when combined with a high fat diet.

Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?

Although dietary fatty acids can modulate metabolic and immune responses, the effects of palmitoleic acid (16:1n-7) remain unclear. Since this monounsaturated fatty acid is described as a lipokine, studies with cell culture and rodent models have suggested it enhances whole body insulin sensitivity, stimulates insulin secretion by ß cells, increases hepatic fatty acid oxidation, improves the blood lipid profile, and alters macrophage differentiation. However, human studies report elevated blood levels of palmitoleic acid in people with obesity and metabolic syndrome. These findings might be reflection of the level or activity of stearoyl-CoA desaturase-1, which synthesizes palmitoleate and is enhanced in liver and adipose tissue of obese patients. The aim of this review is to describe the immune-metabolic effects of palmitoleic acid observed in cell culture, animal models, and humans to answer the question of whether palmitoleic acid is a plausible nonpharmacological strategy to prevent, control, or ameliorate chronic metabolic and inflammatory disorders. Despite the beneficial effects observed in cell culture and in animal studies, there are insufficient human intervention studies to fully understand the physiological effects of palmitoleic acid. Therefore, more human-based research is needed to identify whether palmitoleic acid meets the promising therapeutic potential suggested by the preclinical research.

Evidence for Involvement of IL-9 and IL-22 in Cows' Milk Allergy in Infants.

Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows' milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows' milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.

Palmitoleic acid reduces the inflammation in LPS-stimulated macrophages by inhibition of NFκB, independently of PPARs.

Palmitoleic acid (PM, 16:1n-7) has anti-inflammatory properties that could be linked to higher expression of PPARα, an inhibitor of NFκB. Macrophages play a major role in the pathogenesis of chronic inflammation, however, the effects of PM on macrophages are underexplored. Thus, we aimed to investigate the effects of PM in activated macrophages as well the role of PPARα. Primary macrophages were isolated from C57BL/6 wild type (WT) and PPARα knockout (KO) mice, cultured under standard conditions and exposed to lipopolysaccharides LPS (2.5 µg/ml) and PM 600 µmol/L conjugated with albumin for 24 hours. The stimulation with LPS increased the production of interleukin (IL)-6 and IL-1ß while PM decreased the production of IL-6 in WT macrophages. In KO macrophages, LPS increased the production of tumour necrosis factor (TNF)-α and IL-6 and PM decreased the production of TNFα. The expression of inflammatory markers such NFκB and IL1ß were increased by LPS and decreased by PM in both WT and KO macrophages. PM reduced the expression of MyD88 and caspase-1 in KO macrophages, and the expression of TLR4 and HIF-1α in both WT and KO macrophages, although LPS had no effect. CD86, an inflammatory macrophage marker, was reduced by PM independently of genotype. PM increased PPARγ and reduced PPARß gene expression in macrophages of both genotypes, and increased ACOX-1 expression in KO macrophages. In conclusion, PM promotes anti-inflammatory effects in macrophages exposed to LPS through inhibition of inflammasome pathway, which was independent of PPARα, PPARϒ and AMPK, thus the molecular mechanisms of anti-inflammatory response caused by PM is still unclear.

Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats.

INTRODUCTION: Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. OBJECTIVES: We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. METHODS: Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process. RESULTS: LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αß), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). CONCLUSIONS: Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.

Dietary docosahexaenoic acid and eicosapentaenoic acid influence liver triacylglycerol and insulin resistance in rats fed a high-fructose diet.

This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two groups: Control (C, n = 6) and Fructose (Fr, n = 32), the latter receiving a diet containing 63% by weight fructose for 60 days. After this period, 24 animals from Fr group were allocated to three groups: FrFO2 (n = 8) receiving 63% fructose and 2% FO plus 5% soybean oil; FrFO5 (n = 8) receiving 63% fructose and 5% FO plus 2% soybean oil; and FrFO7 (n = 8) receiving 63% fructose and 7% FO. Animals were fed these diets for 30 days. Fructose led to an increase in liver weight, hepatic and serum triacylglycerol, serum alanine aminotransferase and HOMA1-IR index. These alterations were reversed by 5% and 7% FO. FO had a dose-dependent effect on expression of genes related to hepatic ß-oxidation (increased) and hepatic lipogenesis (decreased). The group receiving the highest FO amount had increased markers of oxidative stress. It is concluded that n-3 fatty acids may be able to reverse the adverse metabolic effects induced by a high fructose diet.