Pro-resolving mediators produced from EPA and DHA: Overview of the pathways involved and their mechanisms in metabolic syndrome and related liver diseases

López‐Vicario, Cristina; Rius, Bibiana; Alcaraz‐Quiles, José; García-Alonso, Verónica; Lopategi, Aritz; Titos, Esther; Clària, Joan

doi:10.1016/j.ejphar.2015.03.092

Cited by 87 publications

(82 citation statements)

References 113 publications

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“…12/15-LOX plays a key role in the regulation of different homeostatic processes as well as in the pathogenesis of several diseases (Uderhardt and Kronke, 2012; Lopez-Vicario et al, 2016). Oxygenated products of unsaturated fatty acids possess immune modulatory properties that effect inflammatory responses (Duvall and Levy, 2016; Whelan et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Oxygenated products of unsaturated fatty acids possess immune modulatory properties that effect inflammatory responses (Duvall and Levy, 2016; Whelan et al, 2016). Several studies investigated the properties and function of fatty acid derivatives, particularly arachidonic acid (AA, C20:4n-6) and DHA (C22:6n-3) and their related metabolic pathways (Lopez-Vicario et al, 2016). Elegant reviews described the pro-inflammatory as well as the inflammatory-resolving functions of various 12/15-LOX products (Kuhn and O'Donnell, 2006; Ackermann et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…An imbalance caused by excessive intake of n-6 fatty acids from the modern Western diet may contribute to several chronic diseases (Lopez-Vicario et al, 2016). Therefore, higher intake of n-3 fatty acids is recommended (Calder, 2008; Beermann et al, 2016; Michalak et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

et al. 2017

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Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z,13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E,12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R*-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14–3.73 μM) and elastase release (IC50 1.26–4.57 μM) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187- and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E,12Z-octadecadienoic acid, IC50 92.4 and 49.7 μM, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

et al. 2017

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“…SPMs, part of a larger family of proresolving molecules, are enzymatically derived from essential fatty acids and can play important roles to restrain inflammation and promote host defences to repair tissue inflammation . They have been proposed to play a role in obesity and the MetS . There is a paucity of information about these molecules and cardiac fibrosis or HFpEF.…”

Section: Omega‐3 and Spms As Potential Therapies For Hfpefmentioning

confidence: 99%

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

Warbrick

Rabkin

2019

Obesity Reviews

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Summary Heart failure with preserved ejection fraction (HFpEF), a common condition with an increased mortality, is strongly associated with obesity and the metabolic syndrome. The latter two conditions are associated with increased epicardial fat that can extend into the heart. This review advances the proposition that hypoxia‐inhibitory factor‐1α (HIF‐1α) maybe a key factor producing HFpEF. HIF‐1α, a highly conserved transcription factor that plays a key role in tissue response to hypoxia, is increased in adipose tissue in obesity. Increased HIF‐1α expression leads to expression of a potent profibrotic transcriptional programme involving collagen I, III, IV, TIMP, and lysyl oxidase. The net effect is the formation of collagen fibres leading to fibrosis. HIF‐1α is also responsible for recruiting M1 macrophages that mediate obesity‐associated inflammation, releasing IL‐6, MCP‐1, TNF‐α, and IL‐1β with increased expression of thrombospondin, pro α2 (I) collagen, transforming growth factor β, NADPH oxidase, and connective tissue growth factor. These factors can accelerate cardiac fibrosis and impair cardiac diastolic function. Inhibition of HIF‐1α expression in adipose tissue of mice fed a high‐fat diet suppressed fibrosis and reduces inflammation in adipose tissue. Delineation of the role played by HIF‐1α in obesity‐associated HFpEF may lead to new potential therapies.

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“…Importantly, such therapeutic approaches would likely have few side effects and provide long-term safety with respect to CVD. The ω3-PUFA-derived SPMs attenuate obesity-induced adipose inflammation and related liver disease [54][55][56][57][58] as well as many features of CVD (for review articles, see [22,40,59,60]). Similarly, AnxA1 correlates with reduced adipose inflammation and protects against nonalcoholic steatohepatitis [61,62].…”

Section: Inflammatory Resolutionmentioning

confidence: 99%

The role of lipoxins in cardiometabolic physiology and disease

Börgeson¹

2016

Cardiovascular Endocrinology

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Pro-resolving mediators produced from EPA and DHA: Overview of the pathways involved and their mechanisms in metabolic syndrome and related liver diseases

Cited by 87 publications

References 113 publications

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

The role of lipoxins in cardiometabolic physiology and disease

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