A 'desaturase hypothesis' for atherosclerosis: Janus-faced enzymes in omega-6 and omega-3 polyunsaturated fatty acid metabolism.
The delta-5 and delta-6 desaturases are key enzymes in the metabolism of omega-3 (omega-3) and omega-6 (omega-6) polyunsaturated fatty acids (PUFA), which in turn influence cellular functions by regulating several metabolic pathways with well-known effects on the cardiovascular system. At present, data about desaturase activity and cardiovascular risk remain inconclusive. In this short review we propose a 'desaturase hypothesis' of atherosclerosis, providing suggestions for the Janus-faced role of desaturases, with both more favorable (mainly related to omega-3 long-chain fatty acids) and more harmful (mainly related to omega-6 long-chain fatty acids) cardiovascular effects than those obtained in subjects with lower desaturase activity. In particular in populations eating a Western diet rich in omega-6 PUFA, a high desaturase activity may promote an increased bioavailability of arachidonic acid with prevailing synthesis of arachidonic acid-derived proinflammatory eicosanoids, finally favoring atherosclerotic vascular damage. In contrast, high desaturase activity in subjects consuming a diet rich in omega-3 PUFA or receiving omega-3 PUFA supplementation could result in the opposite situation with a preferential synthesis of anti-inflammatory eicosanoids. For these reasons, carriers of specific FADS haplotypes may be predisposed to more pronounced vascular inflammatory damage, but also to an increased beneficial effect with omega-3 PUFA supplementation.
Martinelli
Nicola
N
Department of Clinical and Experimental Medicine, University of Verona, Policlinico G.B. Rossi, piazzale L.A. Scuro 10, Verona, Italy.
Consoli
Letizia
L
Olivieri
Oliviero
O
D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D000090943:Delta-5 Fatty Acid Desaturase; D004032:Diet; D004777:Environment; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000627:therapeutic use; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D006801:Humans; D050602:Linoleoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological
D000090943:Delta-5 Fatty Acid Desaturase; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase