Quantifying Conversion of Linoleic to Arachidonic and Other N-6 Polyunsaturated Fatty Acids in Unanesthetized Rats

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2010 Jul 13

PMID 20622136

Citations 9

Authors

Fei Gao

Dale Kiesewetter

Lisa Chang

Stanley I Rapoport

Miki Igarashi

Affiliations

Soon will be listed here.

Abstract

Isotope feeding studies report a wide range of conversion fractions of dietary shorter-chain polyunsaturated fatty acids (PUFAs) to long-chain PUFAs, which limits assessing nutritional requirements and organ effects of arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids. In this study, whole-body (largely liver) steady-state conversion coefficients and rates of circulating unesterified linoleic acid (LA, 18:2n-6) to esterified AA and other elongated n-6 PUFAs were quantified directly using operational equations, in unanesthetized adult rats on a high-DHA but AA-free diet, using 2 h of intravenous [U-(13)C]LA infusion. Unesterified LA was converted to esterified LA in plasma at a greater rate than to esterified gamma-linolenic (gamma-LNA, 18:3n-6), eicosatrienoic acid (ETA, 20:3n-6), or AA. The steady-state whole-body synthesis-secretion (conversion) coefficient k*(i) to AA equaled 5.4 x 10(-3) min(-1), while the conversion rate (coefficient x concentration) equaled 16.1 micromol/day. This rate exceeds the reported brain AA consumption rate by 27-fold. As brain and heart cannot synthesize significant AA from circulating LA, liver synthesis is necessary to maintain their homeostatic AA concentrations in the absence of dietary AA. The heavy-isotope intravenous infusion method could be used to quantify steady-state liver synthesis-secretion of AA from LA under different conditions in rodents and in humans.

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References

Brenner R, Peluffo R . Effect of saturated and unsaturated fatty acids on the desaturation in vitro of palmitic, stearic, oleic, linoleic, and linolenic acids. J Biol Chem. 1966; 241(22):5213-9. View

Rapoport S, Rao J, Igarashi M . Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. Prostaglandins Leukot Essent Fatty Acids. 2007; 77(5-6):251-61. PMC: 2725409. DOI: 10.1016/j.plefa.2007.10.023. View

Das U, Fams . Long-chain polyunsaturated fatty acids in the growth and development of the brain and memory. Nutrition. 2003; 19(1):62-5. DOI: 10.1016/s0899-9007(02)00852-3. View

McArthur M, Atshaves B, Frolov A, Foxworth W, Kier A, Schroeder F . Cellular uptake and intracellular trafficking of long chain fatty acids. J Lipid Res. 1999; 40(8):1371-83. View

Green J, Liu Z, Bazinet R . Brain phospholipid arachidonic acid half-lives are not altered following 15 weeks of N-3 polyunsaturated fatty acid adequate or deprived diet. J Lipid Res. 2009; 51(3):535-43. PMC: 2817583. DOI: 10.1194/jlr.M000786. View

Brash A . Arachidonic acid as a bioactive molecule. J Clin Invest. 2001; 107(11):1339-45. PMC: 209328. DOI: 10.1172/JCI13210. View

Scott B, Bazan N . Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc Natl Acad Sci U S A. 1989; 86(8):2903-7. PMC: 287028. DOI: 10.1073/pnas.86.8.2903. View

Goldberg I . Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res. 1996; 37(4):693-707. View

Kris-Etherton P, Hill A . N-3 fatty acids: food or supplements?. J Am Diet Assoc. 2008; 108(7):1125-30. DOI: 10.1016/j.jada.2008.04.025. View

10.

Gibbons G . Assembly and secretion of hepatic very-low-density lipoprotein. Biochem J. 1990; 268(1):1-13. PMC: 1131384. DOI: 10.1042/bj2680001. View

11.

Carlson S, Carver J, House S . High fat diets varying in ratios of polyunsaturated to saturated fatty acid and linoleic to linolenic acid: a comparison of rat neural and red cell membrane phospholipids. J Nutr. 1986; 116(5):718-25. DOI: 10.1093/jn/116.5.718. View

12.

Innis S . The role of dietary n-6 and n-3 fatty acids in the developing brain. Dev Neurosci. 2000; 22(5-6):474-80. DOI: 10.1159/000017478. View

13.

Igarashi M, Ma K, Chang L, Bell J, Rapoport S . Rat heart cannot synthesize docosahexaenoic acid from circulating alpha-linolenic acid because it lacks elongase-2. J Lipid Res. 2008; 49(8):1735-45. PMC: 6075821. DOI: 10.1194/jlr.M800093-JLR200. View

14.

Brenna J, Salem Jr N, Sinclair A, Cunnane S . alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids. 2009; 80(2-3):85-91. DOI: 10.1016/j.plefa.2009.01.004. View

15.

Funk C . Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001; 294(5548):1871-5. DOI: 10.1126/science.294.5548.1871. View

16.

BEZARD J, Blond J, Bernard A, Clouet P . The metabolism and availability of essential fatty acids in animal and human tissues. Reprod Nutr Dev. 1994; 34(6):539-68. DOI: 10.1051/rnd:19940603. View

17.

DeMar Jr J, Ma K, Bell J, Rapoport S . Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. J Neurochem. 2004; 91(5):1125-37. DOI: 10.1111/j.1471-4159.2004.02789.x. View

18.

Nakamura M, Nara T . Essential fatty acid synthesis and its regulation in mammals. Prostaglandins Leukot Essent Fatty Acids. 2003; 68(2):145-50. DOI: 10.1016/s0952-3278(02)00264-8. View

19.

Leyton J, Drury P, Crawford M . Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. Br J Nutr. 1987; 57(3):383-93. DOI: 10.1079/bjn19870046. View

20.

Hurtado de Catalfo G, Mandon E, de Gomez Dumm I . Arachidonic acid biosynthesis in non-stimulated and adrenocorticotropin-stimulated Sertoli and Leydig cells. Lipids. 1992; 27(8):593-8. DOI: 10.1007/BF02536116. View