Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs

Yamada, Hidetoshi; Oshiro, Eriko; Kikuchi, Susumu; Hakozaki, Mayuka; Takahashi, Hideyuki; Kimura, Ken‐ichi

doi:10.1194/jlr.m047514

Cited by 50 publications

(40 citation statements)

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“…For example, 8‐HEPE was one of the most responsive analytes to EPA feeding, a finding that is consistent with several studies in which human subjects were fed fish oil (57, 60, 70). Although the physiologic significance of these analytes in human blood remains to be determined, 8‐HEPE and 9‐HEPE in krill extracts possess potent bioactivity as PPAR agonists, inducing metabolic responses including stimulation of fatty acid oxidation, adipogenesis, and glucose uptake in vitro (71).…”

Section: Discussionmentioning

confidence: 99%

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

et al. 2016

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In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5 (RvD5) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E (15-keto-PGE). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

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Section: Discussionmentioning

confidence: 99%

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

et al. 2016

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“…Therefore, much attention is aimed at developing novel classes of selective and effective PPARc modulators that preserve the anti-inflammatory activity of PPARc agonists while eliminating many of the unwanted side effects (24,26,27). This strategy (10) Rosiglitazone (141) 15-Hydroxy-eicosatetraenoic acid (142) Pioglitazone (143) 9-and 13-hydroxy-octadecadienoic acid (144) Troglitazone (145) 15-Deoxy 12,14-prostaglandin J2 (146) Ciglitazone (147) Farglitazar (148) S26948 ( aims to uncouple different effects of PPAR ligands, so that they differentially induce specific receptor effects when compared to a full agonist (24,26).…”

Section: Pparc and Skin Inflammationmentioning

confidence: 99%

The role of PPARγ‐mediated signalling in skin biology and pathology: new targets and opportunities for clinical dermatology

Ramot

Mastrofrancesco

Camera

et al. 2015

Experimental Dermatology

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Yuval Ramot and Arianna Mastrofrancesco contributed equally to this work.Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARc-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARc modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARc-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARc ligands and to better understand on the molecular level how PPARc-regulated cutaneous lipid metabolism and PPARcmediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARc modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARc signalling in human skin and its appendages are systematically dissected.

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“…The oxygenated product of EPA, HEPE, was higher in mice fed DHA and CLA concomitantly suggesting that DHA was potent enough to overcome the CLA-induced decrease. The physiological role of HEPE is not clear, but similarly to other n-3 PUFA-derived oxylipins, it is possible that an anti-inflammatory role is involved [67]. We are unable to comment upon the CLA and DHA induced changes in the concentrations of pro-resolving mediators such as resolvins D and E series, protectins, and maresins, because they were not analyzed.…”

Section: Discussionmentioning

confidence: 96%

Dietary Docosahexaenoic Acid and trans‐10, cis‐12‐Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue

Adkins

Belda

Pedersen

et al. 2017

Lipids

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Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some health benefits of n-3 PUFA are mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n-3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA, and putative from CLA were quantified. CLA containing diets reduced AT mass by ~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA-and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA-derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F (P < 0.05), and had mixed effects on ALA-derived alcohols. Dietary CLA lowered EPA-, DHA-, and ALA-derived epoxides, ARA-derived ketones and epoxides, and ALA-derived alcohols. While dietary CLA induced variable effects in EPA-, DHA-, and LNA-derived alcohols and LNA-derived ketones, it elevated ARA-derived alcohols and PGF, PGF, and F2-isoprostanes. DHA counteracted CLA-induced effects in 67, 57, 43, and 29% of total DHA-, ARA-, EPA-, and ALA-derived oxylipins, respectively. Thus, CLA elevated proinflammatory oxylipins while DHA increased anti-inflammatory oxylipins and diminished concentration of CLA-induced pro-inflammatory oxylipins in AT.

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Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs

Cited by 50 publications

References 50 publications

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

The role of PPARγ‐mediated signalling in skin biology and pathology: new targets and opportunities for clinical dermatology

Dietary Docosahexaenoic Acid and trans‐10, cis‐12‐Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue

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