Desaturation and elongation are necessary steps in the modification of the essential fatty acids EFA), linoleic (18:2n6) and linolenic (18:3n3) acids, to arachidonic (20:4n6) and docosahexaenoic (22:6n3) acids, respectively. The levels of the latter two fatty acids are lowered by ethanol consumption in blood cells, liver and brain in animals. We have shown that the mechanisms underlying the disruption of essential fatty acid levels in these tissues are in part due to the inhibition of the elongation/desaturation of 18-carbon essential fatty acids by alcohol. A stable isotope gas chromatography-mass spectrometry (GC-MS) method has been developed that allows for the in vivo examination of these processes. This method has improved the sensitivity of studies in large animals. Studies in mice, rats, cats and rhesus monkeys have suggested that all mammals have elongation and desaturation capability and that heir products may be monitored in the blood supply. Felines, which had been given alcohol for 14 weeks, showed an 80% reduction in 20:4n6 and eicosapentaenoic (20:5n3) acid in the liver and blood together with a decrease in the metabolism of deuterated 18:2n6 and 18:3n3 to deuterated 20:4n6 and 20:5n3, respectively. Our findings show that the feline brain is a unique site of 22:6n3 production in this species, therefore, we are investigating the effects of chronic alcohol exposure on the brain's lipid composition and 22:6n3 formation. Our recent studies indicate specific fats in the diet regulate the synthesis of polyunsaturated fatty acids in carnivores and non-human primates. We have initiated human trials to investigate the effects of diet, and alcohol withdrawal on essential fatty acid metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000262-10
Application #
3789529
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Salem, N M; Lin, Y H; Moriguchi, T et al. (2015) Distribution of omega-6 and omega-3 polyunsaturated fatty acids in the whole rat body and 25 compartments. Prostaglandins Leukot Essent Fatty Acids 100:13-20
Lin, Yu Hong; Shah, Samit; Salem Jr, Norman (2011) Altered essential fatty acid metabolism and composition in rat liver, plasma, heart and brain after microalgal DHA addition to the diet. J Nutr Biochem 22:758-65
DeMar Jr, James C; DiMartino, Carmine; Baca, Adam W et al. (2008) Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats. J Lipid Res 49:1963-80
Polozova, Alla; Salem Jr, Norman (2007) Role of liver and plasma lipoproteins in selective transport of n-3 fatty acids to tissues: a comparative study of 14C-DHA and 3H-oleic acid tracers. J Mol Neurosci 33:56-66
Pawlosky, Robert J; Hibbeln, Joseph R; Salem Jr, Norman (2007) Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers. J Lipid Res 48:935-43
Lin, Yu Hong; Salem Jr, Norman (2007) Whole body distribution of deuterated linoleic and alpha-linolenic acids and their metabolites in the rat. J Lipid Res 48:2709-24
Pawlosky, Robert J; Lin, Yu Hong; Llanos, Adolfo et al. (2006) Compartmental analyses of plasma 13C- and 2H-labeled n-6 fatty acids arising from oral administrations of 13C-U-18:2n-6 and 2H5-20:3n-6 in newborn infants. Pediatr Res 60:327-33
Polozova, Alla; Gionfriddo, Elisa; Salem Jr, Norman (2006) Effect of docosahexaenoic acid on tissue targeting and metabolism of plasma lipoproteins. Prostaglandins Leukot Essent Fatty Acids 75:183-90
Cunnane, Stephen C; Ryan, Mary Ann; Lin, Yu Hong et al. (2006) Suckling rats actively recycle carbon from alpha-linolenate into newly synthesized lipids even during extreme dietary deficiency of n-3 polyunsaturates. Pediatr Res 59:107-10
Lin, Yu Hong; Salem Jr, Norman (2005) In vivo conversion of 18- and 20-C essential fatty acids in rats using the multiple simultaneous stable isotope method. J Lipid Res 46:1962-73

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