Endogenous Production of Long-Chain Polyunsaturated Fatty Acids and Metabolic Disease Risk
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LIPIDS (J ORDOVAS AND L PARNELL, SECTION EDITORS)
Endogenous Production of Long-Chain Polyunsaturated Fatty Acids and Metabolic Disease Risk Harvey J. Murff & Todd L. Edwards
Published online: 16 October 2014 # Springer Science+Business Media New York 2014
Abstract Long-chain polyunsaturated fatty acids (PUFAs) are important structural components of cellular membranes and are converted into eicosanoids which serve various biological roles. The most common dietary n-6 and n-3 PUFAs are linoleic acid and α-linoleic acid, respectively. These 18carbon chain fatty acids undergo a series of desaturation and elongation steps to become the 20-carbon fatty acids arachidonic acid and eicosapentaenoic acid, respectively. Evidence from genome-wide association studies has consistently demonstrated that plasma and tissue levels of the n-6 long-chain PUFA arachidonic acid and to a lesser extent the n-3 longchain PUFA eicosapentaenoic acid are strongly influenced by variation in fatty acid desaturase-1,-2, and elongation of very long-chain fatty acid genes. Studies of functional variants in these genes, as well as studies in which desaturase activity has been indirectly estimated by fatty acid product-to -precursor ratios, have suggested that endogenous capacity to synthesize long-chain PUFAs may be associated with metabolic diseases such as diabetes mellitus. Interventional studies are starting to tease out the complicated relationship between dietary intakes of specific fatty acids, variation in desaturase and elongase genes and tissue levels of long-chain PUFAs. Thus, future studies of dietary PUFA interventions designed to reduce This article is part of the Topical Collection on Lipids H. J. Murff (*) Division of General Internal Medicine and Public Health, Vanderbilt University School of Medicine, 6012 Medical Center East, 1215 21st Avenue South, Nashville, TN 37232-8300, USA e-mail: [email protected] H. J. Murff GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA T. L. Edwards Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN, USA
inflammatory and metabolic diseases will need to carefully consider how an individual’s genetically determined endogenous long-chain PUFA synthesis capacity might modify therapeutic response. Keywords Acids . Polyunsaturated . Fatty acid . Delta 5 desaturase . Fatty acid delta 6 desaturase . Eicosanoids . Diabetes mellitus
Introduction Long-chain polyunsaturated fatty acids (PUFA) are chains of 18 to 22 carbon atoms that contain two or more sequential double bonds. The two predominant classes of PUFAs are n-6 and n-3, categorized based on the position of the first double bond from the methyl end of the carbon chain (n-x nomenclature). In the Western diet, the n-6 PUFA linoleic acid (LA) (18:2n-6) accounts for 84–89 % of total PUFA dietary intake [1]. LA is metabolized to arachidonic acid (ARA) (20:4n-6) through a series of desaturation and elongation reactions. The rate-limiting step in this metabolic pathway
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