Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Apr;86(8):2903–2907. doi: 10.1073/pnas.86.8.2903

Membrane docosahexaenoate is supplied to the developing brain and retina by the liver.

B L Scott 1, N G Bazan 1
PMCID: PMC287028  PMID: 2523075

Abstract

Docosahexaenoic acid [22:6 omega 3; 22:6(4, 7, 10, 13, 16, 19)] is concentrated in phospholipids of cellular membranes from brain and retina. Although linolenic acid [18:3 omega 3; 18:3(9, 12, 15)] is the major omega 3 fatty acid of mouse dams' milk, 22:6 is the prevalent omega 3 fatty acid in serum and tissues. Intraperitoneal injection of [1-14C]18:3 into 3-day-old mouse pups resulted in liver and serum lipid labeling that was initially high, followed by a rapid decline. In contrast, labeling of brain and retinal lipids were initially low and increased with time. Labeled 22:6 first appeared in liver 2 hr after injection and later in brain and retina. We suggest that 22:6 synthesized from 18:3 by the liver is secreted into the bloodstream in lipoproteins, taken up by brain and retina, and incorporated into cell membranes. We hypothesize that the 22:6 requirements of membranes (e.g., during synaptogenesis, photoreceptor membrane biogenesis, or repair after ischemic injury or neurodegenerative disorders) are met by a signal that is sent by the appropriate tissues to the liver to evoke the secretion of 22:6-containing lipoproteins.

Full text

PDF
2903

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aveldano M. I., VanRollins M., Horrocks L. A. Separation and quantitation of free fatty acids and fatty acid methyl esters by reverse phase high pressure liquid chromatography. J Lipid Res. 1983 Jan;24(1):83–93. [PubMed] [Google Scholar]
  2. Aveldaño M. I., Bazán N. G. Differential lipid deacylation during brain ischemia in a homeotherm and a poikilotherm. Content and composition of free fatty acids and triacylglycerols. Brain Res. 1975 Dec 12;100(1):99–110. doi: 10.1016/0006-8993(75)90244-9. [DOI] [PubMed] [Google Scholar]
  3. Aveldaño M. I., Bazán N. G. Displacement into incubation medium by albumin of highly unsaturated retina free fatty acids arising from membrane lipids. FEBS Lett. 1974 Mar 15;40(1):53–56. doi: 10.1016/0014-5793(74)80892-6. [DOI] [PubMed] [Google Scholar]
  4. Bazan N. G., Birkle D. L., Reddy T. S. Docosahexaenoic acid (22:6, n-3) is metabolized to lipoxygenase reaction products in the retina. Biochem Biophys Res Commun. 1984 Dec 14;125(2):741–747. doi: 10.1016/0006-291x(84)90601-6. [DOI] [PubMed] [Google Scholar]
  5. Bazan N. G., Reddy T. S., Redmond T. M., Wiggert B., Chader G. J. Endogenous fatty acids are covalently and noncovalently bound to interphotoreceptor retinoid-binding protein in the monkey retina. J Biol Chem. 1985 Nov 5;260(25):13677–13680. [PubMed] [Google Scholar]
  6. Bazán N. G., Jr Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta. 1970 Oct 6;218(1):1–10. doi: 10.1016/0005-2760(70)90086-x. [DOI] [PubMed] [Google Scholar]
  7. Cook H. W. In vitro formation of polyunsaturated fatty acids by desaturation in rat brain: some properties of the enzymes in developing brain and comparisons with liver. J Neurochem. 1978 Jun;30(6):1327–1334. doi: 10.1111/j.1471-4159.1978.tb10463.x. [DOI] [PubMed] [Google Scholar]
  8. Corey E. J., Shih C., Cashman J. R. Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3581–3584. doi: 10.1073/pnas.80.12.3581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crawford M. A., Hassam A. G., Williams G. Essential fatty acids and fetal brain growth. Lancet. 1976 Feb 28;1(7957):452–453. doi: 10.1016/s0140-6736(76)91476-8. [DOI] [PubMed] [Google Scholar]
  10. Dhopeshwarkar G. A., Subramanian C. Intracranial conversion of linoleic acid to arachidonic acid: evidence for lack of delta8 desaturase in the brain. J Neurochem. 1976 Jun;26(6):1175–1179. doi: 10.1111/j.1471-4159.1976.tb07003.x. [DOI] [PubMed] [Google Scholar]
  11. Fliesler S. J., Anderson R. E. Chemistry and metabolism of lipids in the vertebrate retina. Prog Lipid Res. 1983;22(2):79–131. doi: 10.1016/0163-7827(83)90004-8. [DOI] [PubMed] [Google Scholar]
  12. Holman R. T. Control of polyunsaturated acids in tissue lipids. J Am Coll Nutr. 1986;5(2):183–211. doi: 10.1080/07315724.1986.10720125. [DOI] [PubMed] [Google Scholar]
  13. Lamptey M. S., Walker B. L. A possible essential role for dietary linolenic acid in the development of the young rat. J Nutr. 1976 Jan;106(1):86–93. doi: 10.1093/jn/106.1.86. [DOI] [PubMed] [Google Scholar]
  14. Naughton J. M. Supply of polyenoic fatty acids to the mammalian brain: the ease of conversion of the short-chain essential fatty acids to their longer chain polyunsaturated metabolites in liver, brain, placenta and blood. Int J Biochem. 1981;13(1):21–32. doi: 10.1016/0020-711x(81)90132-4. [DOI] [PubMed] [Google Scholar]
  15. Neuringer M., Connor W. E., Lin D. S., Barstad L., Luck S. Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4021–4025. doi: 10.1073/pnas.83.11.4021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Neuringer M., Connor W. E., Van Petten C., Barstad L. Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest. 1984 Jan;73(1):272–276. doi: 10.1172/JCI111202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nouvelot A., Delbart C., Bourre J. M. Hepatic metabolism of dietary alpha-linolenic acid in suckling rats, and its possible importance in polyunsaturated fatty acid uptake by the brain. Ann Nutr Metab. 1986;30(5):316–323. doi: 10.1159/000177209. [DOI] [PubMed] [Google Scholar]
  18. Reddy T. S., Bazan N. G. Synthesis of arachidonoyl coenzyme A and docosahexaenoyl coenzyme A in retina. Curr Eye Res. 1984 Oct;3(10):1225–1232. doi: 10.3109/02713688409000826. [DOI] [PubMed] [Google Scholar]
  19. Reddy T. S., Bazan N. G. Synthesis of docosahexaenoyl-, arachidonoyl- and palmitoyl-coenzyme A in ocular tissues. Exp Eye Res. 1985 Jul;41(1):87–95. doi: 10.1016/0014-4835(85)90097-1. [DOI] [PubMed] [Google Scholar]
  20. Reddy T. S., Sprecher H., Bazan N. G. Long-chain acyl-coenzyme A synthetase from rat brain microsomes. Kinetic studies using [1-14C]docosahexaenoic acid substrate. Eur J Biochem. 1984 Nov 15;145(1):21–29. doi: 10.1111/j.1432-1033.1984.tb08517.x. [DOI] [PubMed] [Google Scholar]
  21. Rhoads D. E., Ockner R. K., Peterson N. A., Raghupathy E. Modulation of membrane transport by free fatty acids: inhibition of synaptosomal sodium-dependent amino acid uptake. Biochemistry. 1983 Apr 12;22(8):1965–1970. doi: 10.1021/bi00277a035. [DOI] [PubMed] [Google Scholar]
  22. Schwieterman W., Sorrentino D., Potter B. J., Rand J., Kiang C. L., Stump D., Berk P. D. Uptake of oleate by isolated rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut. Proc Natl Acad Sci U S A. 1988 Jan;85(2):359–363. doi: 10.1073/pnas.85.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scott B. L., Racz E., Lolley R. N., Bazan N. G. Developing rod photoreceptors from normal and mutant Rd mouse retinas: altered fatty acid composition early in development of the mutant. J Neurosci Res. 1988;20(2):202–211. doi: 10.1002/jnr.490200209. [DOI] [PubMed] [Google Scholar]
  24. Sinclair A. J. Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat. Lipids. 1975 Mar;10(3):175–184. doi: 10.1007/BF02534156. [DOI] [PubMed] [Google Scholar]
  25. Tinoco J. Dietary requirements and functions of alpha-linolenic acid in animals. Prog Lipid Res. 1982;21(1):1–45. doi: 10.1016/0163-7827(82)90015-7. [DOI] [PubMed] [Google Scholar]
  26. Yau T. M., Sun G. Y. The metabolism of (1-14C)arachidonic acid in the neutral glycerides and phosphoglycerides of mouse brain. J Neurochem. 1974 Jul;23(1):99–104. doi: 10.1111/j.1471-4159.1974.tb06921.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES