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Endogenous Production of Long-Chain Polyunsaturated Fatty Acids and Metabolic Disease Risk

  • Lipids (J Ordovas and L Parnell, Section Editors)
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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 18-carbon 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 long-chain 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 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.

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Acknowledgments

This study was supported by the National Cancer Institute (grants CA143288 and CA160938).

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Harvey Murff received a grant from the NIH. Todd Edwards has no disclosures relating to this work.

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This article does not contain any studies with human or animal subjects performed by the author.

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  1. 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

    Harvey J. Murff

  2. GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA

    Harvey J. Murff

  3. Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Todd L. Edwards

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Murff, H.J., Edwards, T.L. Endogenous Production of Long-Chain Polyunsaturated Fatty Acids and Metabolic Disease Risk. Curr Cardiovasc Risk Rep 8, 418 (2014). https://doi.org/10.1007/s12170-014-0418-1

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