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Emerging mechanisms of organ crosstalk: the role of oxylipins
No full textThere is growing interest in the role of oxylipins in the pathophysiology of several diseases. This is accompanied by a limited but evolving evidence base describing augmented oxylipin concentrations in a range of complications including cardiovascular disease, obesity, liver disease and neurological disorders. Despite this, literature describing oxylipin profiles in blood and multiple organs is inconsistent and the mechanisms by which these profiles are altered, and the relationships between localised tissue and circulating oxylipins is poorly understood. Inflammation and immune response associated with disease, requires communication across organs and physiological systems. For example, inflammation and comorbidities associated with obesity extend beyond the adipose tissue and affect the vascular, hepatobiliary, and digestive systems amongst others. Communication between organs and physiological systems is implicated in the progression of disease as well as maintenance of homeostasis. There is emerging evidence for the role of oxylipins as a mechanism of communication in organ crosstalk but the role of these in orchestrating multiple organ and system responses is poorly understood. Herein, we review evidence to support and describe the role of oxylipins in organ crosstalk via the cardiosplenic and gut-link axis. In addition, we review emerging mechanisms of oxylipin regulation, the gut microbiome and modification using nutritional intervention. Finally, we describe future perspectives for addressing challenges in measurement and interpretation of oxylipin research with focus on the host genome as a modifier of oxylipin profiles and response to dietary lipid intervention
Adipose tissue inflammation in obesity and the influence of marine long chain polyunsaturated omega-3 fatty acids
No full textObesity is an excess of adipose tissue and is linked with increased inflammation that enhances risk of type-2 diabetes and cardiovascular disease. Despite this knowledge, a comprehensive overview of the inflammatory state of subcutaneous white adipose tissue (scWAT), which is the main pool for excess dietary lipid storage and plays a major role in whole body endocrine processes, is not reported for humans, particularly in those in which metabolic syndrome is yet to manifest. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been widely examined for their anti-inflammatory effects including modulating gene expression and secretion of systemic inflammatory markers. The research described in this thesis explores scWAT fatty acid (FA) and lipid metabolite composition, the whole tissue transcriptome, protein expression, enzyme activity, and tissue morphology in metabolically healthy obese individuals in comparison to normal weight individuals to provide a comprehensive overview of the inflammatory and metabolic state of the tissue in this condition. Furthermore, it explores the anti-inflammatory potential of a 12-week fish oil (FO) intervention on these tissue parameters. Metabolically healthy obesity (MHO) was associated with an altered FA composition and lipid metabolite profile of scWAT. There was a lower proportion of saturated fatty acids, a higher proportion of monounsaturated fatty acids (MUFA), a higher proportion of arachidonic acid (AA) and concentrations of respective oxylipins and COX-2 protein, lower concentrations of DHA oxylipins, and an alteration of the endocannabinoid system (ECS). MHO was further associated with an altered transcriptome suggestive of enhanced inflammation, immune response, tissue remodelling and expansion, altered lipid and carbohydrate metabolism, and lipid mobilization. This was concordant with tissue morphology which showed evidence of adipocyte hypertrophy and the presence of macrophages arranged in crown like structures. Chronic supplementation with EPA+DHA increased concentrations of sWAT omega-3 FAs and derived oxylipins and decreased AA oxylipins, with an effect on the ECS predominantly in normal weight individuals. EPA+DHA modulated the scWAT transcriptome suggesting promotion of tissue remodelling and down regulation of cell differentiation and the chronic inflammatory response, but to a lesser extent in MHO than in normal weight individuals. This lesser effect in MHO may be explained by several processes observed to be altered in MHO at study entry including mobilization and metabolism of EPA and DHA, in addition to greater proportions of omega-6 PUFA which persisted after 12-week FO intervention. The ratio of omega-6:omega-3 FA is of importance and therefore, greater concentrations of EPA and DHA may be required in these individuals to alter this ratio and subsequent oxylipin synthesis and transcriptome modulation. These data suggest MHO is associated with enhanced sWAT inflammation in the context of tissue expansion, remodelling, and alteration to lipid metabolism and signalling. Furthermore, the data suggest that sWAT from metabolically healthy obese individuals without metabolic syndrome maintains some degree of normal function in that it is not fibrotic and is sensitive to dietary lipid manipulation. EPA+DHA modulated synthesis of EPA, DHA and AA derived oxylipins and the transcriptome but resistance to these effects, particularly on the ECS, was exhibited in MHO
A novel omega-3 glyceride mixture enhances enrichment of EPA and DHA after single dosing in healthy older adults: Results from a double-blind crossover trial
No full textA glyceride mixture of monoglyceride, diglyceride and TAG increases solubilisation and enhances emulsification of n-3 fatty acid (FA)-containing lipids in the stomach. This allows for better access of digestive enzymes, pivotal for the release of bioactive n-3 FA. The objective was to compare the effect of a glyceride formulation and an ethyl ester formulation of EPA + DHA on concentrations of EPA and DHA in plasma following single dosing. We conducted a double-blind crossover trial in which twenty healthy adults aged 50-70 years consumed a single dose (2·8 g EPA + DHA) of each EPA + DHA formulation without a meal in random order separated by a 2-week washout period. EPA and DHA were measured in plasma total lipid over the following 12 h. EPA and DHA in plasma total lipid increased over 12 h with both formulations. A 10-fold greater Δ concentration of EPA, 3-fold greater Δ concentration of DHA and 5-fold greater Δ concentration of EPA + DHA were seen with the glyceride-EPA + DHA. The time at which the maximal concentrations of n-3 FA occurred was 4 h earlier for EPA, 1 h earlier for DHA and 2 h earlier for EPA + DHA when consuming glyceride-EPA + DHA. A mixture of monoglyceride, diglyceride and TAG results in greater and faster incorporation of EPA and DHA into blood plasma lipid in the absence of a fatty meal. This may provide benefit to individuals on a low-fat diet or with digestive impairments and could result in greater efficacy in clinical trials using n-3 FA
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High dose fish oil supplements are more effective than oily fish in altering the number and function of extracellular vesicles in healthy human subjects: a randomized, double-blind, placebo-controlled, parallel trial
Full text linkBackground: N-3 polyunsaturated fatty acids (n-3 PUFAs) delivered by fish oil supplements alter the number and functions of circulating extracellular vesicles (EVs), but consumption of oily fish does not reproduce this effect.
Objective: To assess the effects of fish oil supplements and oily fish, at a level achievable in the diet, on EV numbers, composition and procoagulant activity in healthy human volunteers.
Methods: Forty-two healthy subjects were assigned to one of three treatment groups: (i) fish oil supplements plus white fish meals, (ii) control supplements plus oily fish meals or (iii) control supplements plus white fish meals for 12 weeks in a randomized, double-blind, placebo-controlled, parallel trial. Circulating EVs were enumerated and their procoagulant activity assessed using thrombin generation and fibrinolysis assays.
Results: Fish oil supplements decreased circulating EV numbers and reduced EV-stimulated thrombin generation, but the consumption of oily fish at half the dose of EPA had no effect on either EV number or thrombogenic capacity. Consumption of both oily fish and fish oil supplements increased the EPA and DHA contents of EVs and the proportion of EPA in circulating EVs was strongly associated with EV-stimulated thrombin generation.
Conclusions: The additional 1 g/d EPA delivered in the fish oil supplements is required to decrease the numbers and thrombogenic capacity of EVs, since oily fish at a level achievable in the diet had no effect. Increasing EPA intake beyond current guidelines for oily fish consumption may therefore be required for cardiovascular benefits relating to EVs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice
No full textDelayed 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
The use of gas chromatography to analyze compositional changes of fatty acids in rat liver tissue during pregnancy
No full textPregnancy leads to significant changes to the fatty acid composition of maternal tissues. Lipid profiles can be obtained via gas chromatography to allow identification and quantification of fatty acids in individual lipid classes among rats fed various high and low fat diets during pregnanc
Yeast-derived beta 1,3/1,6 glucan, upper respiratory tract infection and innate immunity in older adults
No full textThe use of gas chromatography to analyse compositional changes of fatty acids in rat liver tissue during pregnancy
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