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Oxidative Stress and Inflammation in Non-communicable Diseases - Molecular Mechanisms and Perspectives in Therapeutics pp 61–81Cite as

Delta-5 and Delta-6 Desaturases: Crucial Enzymes in Polyunsaturated Fatty Acid-Related Pathways with Pleiotropic Influences in Health and Disease

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 824))

Abstract

Polyunsaturated fatty acids (PUFA) play pleiotropic and crucial roles in biological systems. Both blood and tissue levels of PUFA are influenced not only by diet, but to a large extent also by genetic heritability. Delta-5 (D5D) and delta-6 desaturases (D6D), encoded respectively by FADS1 and FADS2 genes, are the rate-limiting enzymes for PUFA conversion and are recognized as main determinants of PUFA levels. Alterations of D5D/D6D activity have been associated with several diseases, from metabolic derangements to neuropsychiatric illnesses, from type 2 diabetes to cardiovascular disease, from inflammation to tumorigenesis. Similar results have been found by investigations on FADS1/FADS2 genotypes. Recent genome-wide association studies showed that FADS1/FADS2 genetic locus, beyond being the main determinant of PUFA, was strongly associated with plasma lipids and glucose metabolism. Other analyses suggested potential link between FADS1/FADS2 polymorphisms and cognitive development, immunological illnesses, and cardiovascular disease. Lessons from both animal models and rare disorders in humans further emphasized the key role of desaturases in health and disease. Remarkably, some of the above mentioned associations appear to be influenced by the environmental context/PUFA dietary intake, in particular the relative prevalence of ω-3 and ω-6 PUFA. In this narrative review we provide a summary of the evidences linking FADS1/FADS2 gene variants and D5D/D6D activities with various traits of human physiopathology. Moreover, we focus also on the potentially useful therapeutic application of D5D/D6D activity modulation, as suggested by anti-inflammatory and tumor-suppressing effects of D6D inhibition in mice models.

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    1. Department of Medicine, University of Verona, Piazzale Luduvico Antonio Scuro, 10, 37134, Verona, Italy

      Federica Tosi, Filippo Sartori, Patrizia Guarini, Oliviero Olivieri & Nicola Martinelli

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      Jordi Camps

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    Tosi, F., Sartori, F., Guarini, P., Olivieri, O., Martinelli, N. (2014). Delta-5 and Delta-6 Desaturases: Crucial Enzymes in Polyunsaturated Fatty Acid-Related Pathways with Pleiotropic Influences in Health and Disease. In: Camps, J. (eds) Oxidative Stress and Inflammation in Non-communicable Diseases - Molecular Mechanisms and Perspectives in Therapeutics. Advances in Experimental Medicine and Biology, vol 824. Springer, Cham. https://doi.org/10.1007/978-3-319-07320-0_7

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