Diversity of lipid mediators in human adipose tissue depots

Clària, Joan; Nguyen, Binh; Madenci, Arin L.; Ozaki, C. Keith; Serhan, Charles N.

doi:10.1152/ajpcell.00351.2012

Cited by 114 publications

(98 citation statements)

References 45 publications

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“…Our results document that 13-DHAHLA has the ability to affect immune cells, alleviate macrophage activation, and stimulate the proresolving processes. It is conceivable that DHAHLA may contribute to the anti-inflammatory and proresolving effects attributed to the DHA in human and murine WAT (lower density of crown-like structures, lower local concentration of proinflammatory cytokines), as was already documented for the other DHA metabolites, namely, docosanoids and related endocannabinoids (24)(25)(26)(27)(28)(29)(30)32). The expression of FAHFA hydrolases in WAT, liver, isolated adipocytes, and SVCs revealed that FAHFA degradation is probably regulated on both local and systemic levels.…”

Section: Discussionmentioning

confidence: 89%

“…In addition, DHAderived lipid mediators such as resolvin D1 have been reported to decrease WAT inflammation, shifting macrophage polarization toward the M2 form and improving insulin sensitivity in obese mice (24)(25)(26)(27). A wide range of lipid mediators, including resolvins D1 and D2, protectin D1, lipoxin A4, 17-hydroxydocosahexaenoic acid (HDHA), 18-HEPE, and 14-HDHA were identified in human subcutaneous WAT, whereas the levels of protectin D1 and 17-HDHA decreased in the subcutaneous WAT of patients with peripheral vascular disease (32). Protectin DX, also known to be produced in WAT, alleviated insulin resistance in db/db mice, but did not resolve WAT inflammation (33).…”

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confidence: 99%

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Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

et al. 2016

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White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids—lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

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Section: Discussionmentioning

confidence: 89%

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confidence: 99%

Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

et al. 2016

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“…Furthermore, levels of RvD2 were 3-to 4-fold higher than RvD1 in these tissues, and signifi cantly higher than levels found in human adipose tissue (approximately 170-to 300-fold) ( 31 ). Specifi c cell surface-binding sites for RvD1 (G protein-coupled receptor 32 and lipoxin A 4 receptor) ( 36 ) have been identifi ed in human leukocytes; however, whether these receptors are present in the placenta is currently unknown.…”

Section: Plasma Pro-infl Ammatory Cytokine Levelsmentioning

confidence: 95%

Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta

Jones

Mark

Keelan

et al. 2013

Journal of Lipid Research

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“…In this respect, biosynthesis of protectin D1 by eosinophils is reduced in patients with severe asthma ( 12 ). MaR-1 has been identifi ed in synovial fl uid of patients with rheumatoid arthritis ( 13 ) and RvD1 and RvD2 have been identifi ed in adipose tissue of healthy patients, whereas PD1 and 17-HDHA are reduced in subcutaneous adipose tissue of patients with peripheral artery disease ( 14 ).…”

Section: Separation Of Spms Using Reverse Phase Lc/ms/msmentioning

confidence: 99%

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

Barden

Mas

Croft

et al. 2014

Journal of Lipid Research

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the infl ammatory process ( 1, 2 ), acting on a number of G-coupled protein receptors, including the leukotriene B4 (LTB 4 ) receptor to affect resolution of infl ammation.Metabolism of EPA by acetylated cyclooxygenase (COX)-2 or cytochrome P450 monooxygenase results in the formation of 18-hydroxyeicosapentaenoic acid (18-HEPE) that can be converted by 5-lipoxygenase (LOX) to 5-hydroperoxy-18-hydroxyeicosapentaenoic acid (5-Hp-18-HEPE). The latter can undergo epoxidation and enzyme hydrolysis to yield resolvin E1 (RvE1), or reduction to yield resolvin E2 (RvE2). A third E-series resolvin, resolvin E3 (RvE3), is generated from EPA by the 12/15 LOX pathway ( 3 ). Studies using chiral chromatography indicate that acetylation of COX-2 by aspirin generates both 18S-HEPE and 18R-HEPE and their respective downstream E-series resolvins 18S-RvE1 and 18R-RvE1 ( 4 ).Metabolism of DHA by either acetylated COX-2 or 15-LOX gives rise to 17-hydroperoxydocosahexaenoic acid (17-HpDHA) that is converted to 17-hydroxydocosahexaenoic acid (17-HDHA). 15-LOX gives rise to mainly 17S-HpDHA whereas acetylated COX-2 yields 17R-HpDHA ( 5 ). The action of 5-LOX on 17-HDHA generates the Dseries resolvins RvD1-RvD6 ( 1 ). In the absence of 5-LOX, protectin D1 (PD1) is formed from 17-HpDHA. In macrophages, 12/15-LOX can act on DHA to form 14-hydroperoxydocosahexaenoic acid (14-HpDHA) that can be further metabolized to 14-hydroxydocosahexaenoic acid (14-HDHA) and the maresins ( 6 ).Most of the research on the effects of SPMs has been in animal models. The resolvins and protectins have been Abstract Resolution of infl ammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.4g/day) for 7 days with random assignment to take aspirin (300 mg/day) or placebo from day 5 to day 7. Blood was collected at baseline (day 0 There is increasing interest in the role of the specialized proresolving mediators (SPMs) that actively stimulate resolution of infl ammation ( 1 ). In particular, recent attention has focused on those SPM derived from the long-chain n-3 fatty acids EPA and DHA. The SPMs formed from EPA are known as E-series resolvins, while those formed from DHA include protectins, D-series resolvins, and maresins ( 1 ). Studies have shown that SPMs increase with time during A.B., T.A.M.,)

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Diversity of lipid mediators in human adipose tissue depots

Cited by 114 publications

References 45 publications

Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

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