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      A Combination of (ω–3) Polyunsaturated Fatty Acids, Polyphenols and L-Carnitine Reduces the Plasma Lipid Levels and Increases the Expression of Genes Involved in Fatty Acid Oxidation in Human Peripheral Blood Mononuclear Cells and HepG2 Cells

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          Abstract

          Background: Hyperlipidemia and obesity are associated with metabolic syndrome and increased risk in developing diabetes and cardiovascular disease. Nutritional supplements, e.g. L-carnitine and polyunsaturated fatty acids (PUFAs), exert lipid-lowering effects. Hence, the hypothesis that dietetic intervention reduces plasma lipid levels and metabolic enzymes in overweight hyperlipidemic subjects was tested. Subjects and Methods: In a prospective placebo-controlled double-blind study in 22 moderately hyperlipidemic obese humans consuming low-fat yoghurt enriched with a combination of low-dose PUFAs, polyphenols and L-carnitine (PPC) twice a day for 12 weeks were compared to 20 matching participants ingesting low-fat yoghurt. The effects on plasma lipids and expression of enzymes involved in regulation of fatty acid oxidation in peripheral blood mononuclear cells (PBMCs) and HepG2 cells were evaluated. Results: PPC consumption led to significantly reduced plasma free fatty acid (–29%) and triglyceride (–24%) concentrations (each p < 0.05). PPC application increased significantly peroxisome proliferator-activated receptor α (PPARα) mRNA abundances and those of PPARα target genes (carnitine palmitoyltransferases-1, CPT1A and CPT1B, carnitine acetyltransferase and organic cation transporter 2; each p < 0.05) in PBMCs. In controls, plasma lipid levels and PBMC gene expression did not change. These findings were substantiated by the results of cell culture experiments in HepG2 cells. Conclusion: Supplementation of PPC had marked lipid-lowering effects and PBMC gene expression profiles seemed to reflect nutrition-related metabolic changes.

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          Peroxisome proliferator-activated receptor alpha target genes.

          Peroxisome proliferator-activated receptors (PPARs) are nuclear proteins that belong to the superfamily of nuclear hormone receptors. They mediate the effects of small lipophilic compounds such as long-chain fatty acids and their derivatives on transcription of genes commonly called PPAR target genes. Here we review the involvement of PPARalpha in peroxisomal and mitochondrial fatty acid oxidation, microsomal fatty acid hydroxylation, lipoprotein, bile and amino acid metabolism, glucose homeostasis, biotransformation, inflammation control, hepato-carcinogenesis and other pathways, through a detailed analysis of the different known or putative PPARalpha target genes.
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            Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects.

            Carnitine palmitoyltransferase (CPT) deficiencies are common disorders of mitochondrial fatty acid oxidation. The CPT system is made up of two separate proteins located in the outer (CPT1) and inner (CPT2) mitochondrial membranes. While CPT2 is an ubiquitous protein, three tissue-specific CPT1 isoforms--the so-called "liver" (CPT1-A), "muscle" (CPT1B) and (CPT1-C) CPT1s--have been shown to exist. Amino acid and cDNA nucleotide sequences have been identified for all of these proteins. CPT1-A deficiency presents as recurrent attacks of fasting hypoketotic hypoglycemia. Twenty four CPT1A mutations have been reported to date. CPT1-B and -C deficiencies have not been hitherto identified. CPT2 deficiency has several clinical presentations. The "benign" adult form (more than 200 families reported) is characterized by episodes of rhabdomyolysis triggered by prolonged exercise. The prevalent S113L mutation is found in about 50% of mutant alleles. The infantile-type CPT2 presents as severe attacks of hypoketotic hypoglycemia, occasionally associated with cardiac damage commonly responsible for sudden death before 1 year of age. In addition to these symptoms, features of brain and kidney dysorganogenesis are frequently seen in the neonatal-onset CPT2 deficiency, almost always lethal during the first month of life. Around 40 CPT2 mutations (private missense or truncating mutations) have hitherto been detected. Treatment is based upon avoidance of fasting and/or exercise, a low fat diet enriched with medium chain triglycerides and carnitine. Prenatal diagnosis may be offered for pregnancies at a 1/4 risk of infantile/severe-type CPT2 deficiency.
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              Polyphenolic phytochemicals--just antioxidants or much more?

              Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A 'recommended' human diet contains significant quantities of polyphenolics, as they have long been assumed to be 'antioxidants' that scavenge excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also have 'indirect' antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last 2-3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects and regulatory effects on energy metabolism and gut health.
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                Author and article information

                Journal
                ANM
                Ann Nutr Metab
                10.1159/issn.0250-6807
                Annals of Nutrition and Metabolism
                S. Karger AG
                0250-6807
                1421-9697
                2011
                June 2011
                29 April 2011
                : 58
                : 2
                : 133-140
                Affiliations
                aCenter for Pathobiochemistry and Genetics, Institute of Medical Chemistry and bDivision of Endocrinology and Metabolism, Internal Medicine 3, Medical University of Vienna, and c3rd Department of Medicine, Hanusch Hospital, Vienna, dHealth Care Center Pielachtal, Frankenfels, eUniversity of Applied Sciences, Wiener Neustadt, and fPharm-Analyt, Baden, Austria
                Author notes
                *A. Lohninger, Center for Pathobiochemistry and Genetics, Institute of Medical Chemistry, Medical University of Vienna, Währingerstrasse 10, AT–1090 Vienna (Austria), Tel. +43 1 4277 60873, E-Mail alfred.lohninger@meduniwien.ac.at
                Article
                327150 Ann Nutr Metab 2011;58:133–140
                10.1159/000327150
                21540583
                9af78cfa-0c76-4446-ba16-566dfd3a91c3
                © 2011 S. Karger AG, Basel

                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
                : 30 June 2010
                : 07 March 2011
                Page count
                Figures: 4, Tables: 2, Pages: 8
                Categories
                Original Paper

                Nutrition & Dietetics,Health & Social care,Public health
                Gene expression,Carnitine,Peripheral blood mononuclear cells,HepG2 cells,ωߝ3 polyunsaturated fatty acids,Polyphenols,Plasma lipids

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