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      Increased FADS2-Derived n-6 PUFAs and Reduced n-3 PUFAs in Plasma of Atopic Dermatitis Patients

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          Abstract

          Fatty acid concentrations, in particular n-3 and n-6 polyunsaturated fatty acids (PUFAs), have been described to be dysregulated in atopic dermatitis (AD) patients. The role of genetic polymorphisms of fatty acid enzymes in AD is controversial. We determined in a Hungarian cohort of healthy volunteers (n = 20) and AD patients (n = 20) triglyceride-, sterol- and phospholipid-bound fatty acids in the plasma, mRNA expression of fatty acid desaturase 2 (FADS2) and stearoyl-coenzyme A desaturase 1 in peripheral blood mononuclear cells (PBMCs) and FADS2 concentrations in plasma. We observed higher levels of monounsaturated fatty acids, 16:1 versus 16:0 ratios in phospholipids, triglycerides and sterol esters in patients compared to healthy subjects. In addition higher levels of the FADS2-derived n-6 PUFAs γ-linolenic acid and dihomo-γ-linolenic acid were observed in PBMCs of patients as well as lower levels of n-3 PUFAs. We conclude that the increased expression of FADS2 in PBMCs, as a representative tissue accessible from human blood of AD patients, might be responsible for higher levels of FADS2-derived n-6 PUFAs and lower n-3 PUFA levels in patients.

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          Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.

          Haiming Cao, Kristin A. Gerhold, Jared Mayers … (2008)
          Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.
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            Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases.

            Manabu T Nakamura, Takayuki Nara (2004)
            Fatty acid desaturases introduce a double bond in a specific position of long-chain fatty acids, and are conserved across kingdoms. Degree of unsaturation of fatty acids affects physical properties of membrane phospholipids and stored triglycerides. In addition, metabolites of polyunsaturated fatty acids are used as signaling molecules in many organisms. Three desaturases, Delta9, Delta6, and Delta5, are present in humans. Delta-9 catalyzes synthesis of monounsaturated fatty acids. Oleic acid, a main product of Delta9 desaturase, is the major fatty acid in mammalian adipose triglycerides, and is also used for phospholipid and cholesteryl ester synthesis. Delta-6 and Delta5 desaturases are required for the synthesis of highly unsaturated fatty acids (HUFAs), which are mainly esterified into phospholipids and contribute to maintaining membrane fluidity. While HUFAs may be required for cold tolerance in plants and fish, the primary role of HUFAs in mammals is cell signaling. Arachidonic acid is required as substrates for eicosanoid synthesis, while docosahexaenoic acid is required in visual and neuronal functions. Desaturases in mammals are regulated at the transcriptional level. Reflecting overlapping functions, three desaturases share a common mechanism of a feedback regulation to maintain products in membrane phospholipids. At the same time, regulation of Delta9 desaturase differs from Delta6 and Delta5 desaturases because its products are incorporated into more diverse lipid groups. Combinations of multiple transcription factors achieve this sophisticated differential regulation.
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              Clinical Validation and Guidelines for the SCORAD Index: Consensus Report of the European Task Force on Atopic Dermatitis

              B. Kunz, J.-F. Stalder, L Labrèze … (2004)
              Article 0 comments Cited 147 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (publisher-id): SPP
                Journal ID (nlm-ta): Skin Pharmacol Physiol
                Journal ID (doi): 10.1159/issn.1660-5527
                Title: Skin Pharmacology and Physiology
                Publisher: S. Karger AG
                ISSN (Print): 1660-5527
                ISSN (Electronic): 1660-5535
                Publication date Subscription-year: 2014
                Publication date (Print): July 2014
                Publication date (Electronic): 20 May 2014
                Volume: 27
                Issue: 5
                Pages: 242-248
                Affiliations
                Departments of aBiochemistry and Molecular Biology and bDermatology, University of Debrecen, cApoptosis and Genomics Research Group of the Hungarian Academy of Science and dPaprika Bioanalytics Bt., Debrecen, and eDepartment of Pediatrics, University of Pecs, Hungary; fHuman Nutrition, School of Medicine, MVLS, University of Glasgow, Glasgow, UK
                Author notes
                *Dr. Ralph Rühl, Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, HU-4032 Debrecen (Hungary), E-Mail ralphruehl@web.de
                Article
                Publisher ID: 358290 Other ID: Skin Pharmacol Physiol 2014;27:242-248
                DOI: 10.1159/000358290
                PubMed ID: 24854601
                SO-VID: 2a7de535-47be-4ddb-8e29-9e3f15fd931f
                Copyright © © 2014 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 19 March 2013
                Date accepted : 02 January 2014
                Page count
                Figures: 2, Tables: 2, Pages: 7
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Keywords: n–3 polyunsaturated fatty acids,Atopic dermatitis, Fatty acid desaturase 2,Lipid enzymes,n–6 polyunsaturated fatty acids
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Dermatology, Pharmacology & Pharmaceutical medicine
                Keywords: n–3 polyunsaturated fatty acids, Atopic dermatitis, Fatty acid desaturase 2, Lipid enzymes, n–6 polyunsaturated fatty acids

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