Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-27T14:36:59.211Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of experimental folate deficiency on lipid metabolism in liver and brain

Published online by Cambridge University Press:  04 June 2009

B. Åkesson ,
C. Fehling ,
M. Jägerstad  and
U. Stenram
B. Åkesson
Affiliation:
Department of Clinical Chemistry, Department of Neurology, Department of Nutrition and Department of Pathology, University of Lund, Lund, Sweden
C. Fehling
Affiliation:
Department of Clinical Chemistry, Department of Neurology, Department of Nutrition and Department of Pathology, University of Lund, Lund, Sweden
M. Jägerstad
Affiliation:
Department of Clinical Chemistry, Department of Neurology, Department of Nutrition and Department of Pathology, University of Lund, Lund, Sweden
U. Stenram
Affiliation:
Department of Clinical Chemistry, Department of Neurology, Department of Nutrition and Department of Pathology, University of Lund, Lund, Sweden
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

1. Rats were given a purified folate-deficient diet containing 5 g succinylsulphathiazole/kg for 4–5 months in two experiments. Control rats were supplemented with folic acid in the drinking-water.

2. Weight gain was much below normal in the folate-deprived rats after the first month. Very low folate levels were recorded in blood, liver and peripheral nerve (12–33% of control). In Ihe central nervous system, including the cerebrospinal fluid, the folate depletion was less conspicuous (50–80% of control). Only marginal signs of anaemia were found and no signs of neurological dysfunction were detected, using nerve conduction velocity measurement and co-ordination tests.

3. Light and electron microscopy of the folate deficient liver revealed fatty infiltration, and enlargement of liver parenchymal cells, nuclei and nucleoli. There was often a considerable amount of bile ductular cells in the lobuli but no cirrhosis. The morphological changes resembled those observed in choline deficiency.

4. Phospholipid N-methylation in liver was depressed in folate deficiency. This was probably due to a decreased availability of S-adenosylmethionine caused by the low concentrations of methylated folate in liver. Intraperitoneal administration of methionine did not normalize phospholipid methylation.

5. In folate deficiency the proportion of ethanolamine phosphoglyceride in liver was increased at the expense of choline phosphoglyceride, which is consistent with a decreased phospholipid methylation. Also an increase in liver triacylglycerol was noted, in accordance with the morphological observations. Brain lipid composition was unchanged.

6. After the injection of labelled ethanolamine, isotope accumulated in liver phosphoethanolamine in folate deficiency, probably due to an impairment of the CTP: ethanolaminephosphate cytidylyltransferase(EC 2.7.7.14) reaction. The mechanism of this impairment is discussed.

7. Although the low concentrations of folate was the main nutritional change in the deprived animals, changes with respect to vitamin B12 and maybe also choline cannot be excluded. We conclude that some of the changes in folate deficiency, i.e. fatty liver and decreased biosynthesis of liver phospholipids may be due to a precipitated deficiency of lipotropic agents, whereas other differences may be specific for deficiency of folate per se, such as changes in liver phospholipid fatty acids and some of the morphological aberrations.

Type
Papers on General Nutrition
Information
British Journal of Nutrition , Volume 47 , Issue 3 , May 1982 , pp. 505 - 520
Copyright
Copyright © The Nutrition Society 1982

References

Åkesson, B. (1978). FEBS Lett. 92, 177.CrossRefGoogle Scholar
Åkesson, B. (1980). In Membrane Fluidity: Biophysical Techniques and Cellular Regulation, p. 419 [Kates, M. and Kuksis, A., editor]. Clifton, N.J.: The Humana Press.CrossRefGoogle Scholar
Åkesson, B., Fehling, C. & Jägerstad, M. (1978). Br. J. Nutr. 40, 521.CrossRefGoogle Scholar
Åkesson, B., Fehling, C. & Jägerstad, M. (1979). Br. J. Nutr. 41, 263.CrossRefGoogle Scholar
Åkesson, B. & Sundler, R. (1977). Biochem. Soc. Trans. 5, 43.CrossRefGoogle Scholar
Alperin, J. B. & Haggard, M. E. (1970). Clin. Res. 18, 40.Google Scholar
Annino, J. S. (1961). In Standard Methods of Clinical Chemistry, vol. 3, p. 200 [Seligson, D., editor]. New York: Academic Press.Google Scholar
Beare-Rogers, J. L. (1971). Lipids 6, 649.CrossRefGoogle Scholar
Crews, F. T., Hirata, F. & Axelrod, J. (1980). J. Neurochem. 34, 1491.CrossRefGoogle Scholar
Custer, R. P., Freeman-Narrod, M. & Narrod, S. A. (1977). J. natn. Cancer Inst. 58, 1011.CrossRefGoogle Scholar
Fallon, H. J., Gertman, P. M. & Kemp, E. L. (1969). Biochim. biophys. Acta 187, 94.CrossRefGoogle Scholar
Fehling, C., Abdulla, M., Brun, A., Dictor, M., Schütz, A. & Skerfving, S. (1975). Toxic. appl. Pharmac. 33, 27.CrossRefGoogle Scholar
Fehling, C. & Jägerstad, M. (1978). Nutr. Metab. 22, 90.CrossRefGoogle Scholar
Fehling, C. & Jägerstad, M. (1979). In Folic Acid in Neurology, Psychiatry, and Internal Medicine, p. 517 [Botez, M. I. and Reynolds, E. H., editors]. New York: Raven Press.Google Scholar
Fehling, C., Jägerstad, M., Åkesson, B., Axelsson, J. & Brun, A. (1978). Br. J. Nutr. 39, 501.CrossRefGoogle Scholar
Fehling, C., Jägerstad, M., Lindstrand, K. & Elmquist, D. (1976). Z. Ernährungswiss 15, 1.CrossRefGoogle Scholar
Forshaw, A. J. (1969). J. clin. Path. 22, 551.CrossRefGoogle Scholar
Garton, G. H., Scaife, J. R., Smith, A. & Siddons, R. C. (1975). Lipids 10, 855.CrossRefGoogle ScholarPubMed
Glenn, J. L. & Austin, W. (1971). Biochim. biophys. Acta 231, 153.CrossRefGoogle Scholar
Grisham, J. W., Banson, B. B. & Hartroft, W. S. (1960). Archs Path. 70, 50.Google Scholar
Grisham, J. W. & Hartroft, W. S. (1961). Lab. Invest. 10, 317.Google Scholar
Haines, D. S. M. & Rose, C. I. (1970). Can. J. Biochem. 48, 885.CrossRefGoogle Scholar
Hale, O. M. & Schaefer, A. E. (1951). Proc. Soc. exp. Biol. Med. 77, 633.CrossRefGoogle Scholar
Halsted, C. H. & Tamura, T. (1979). In Problems in Liver Disease, p. 91 [Davidson, C. S. and Stratton, H. M., editors]. New York: Academic Press.Google Scholar
Haltia, M. (1970). Br. J. exp. Path. 51, 191.Google Scholar
Hirata, F. & Axelrod, J. (1980). Science, N. Y. 209, 1082.CrossRefGoogle Scholar
Hirono, H. & Wada, Y. (1978). J. Nutr. 108, 766.CrossRefGoogle Scholar
Hoffman, D. R., Cornatzer, W. E. & Duerre, J. A. (1979). Can. J. Biochem. 57, 56.CrossRefGoogle Scholar
Jägerstad, M., Åkesson, B. & Fehling, C. (1980). Br. J. Nutr. 44, 361.CrossRefGoogle Scholar
Kodicek, E. & Carpenter, K. J. (1950 a). Blood 5, 540.CrossRefGoogle Scholar
Kodicek, E. & Carpenter, K. J. (1950 b). Blood 5, 522.CrossRefGoogle Scholar
Laird, R. D., McCormick, H. M. & Drill, V. A. (1965). Toxic. appl. Pharmac. 7, 247.CrossRefGoogle Scholar
Lucas, C. C. & Ridout, J. H. (1967). Progr. Chem. Fats Other Lipids 10, 1.CrossRefGoogle Scholar
Lyman, R. L., Sheehan, G. & Tinoco, J. (1971). Can. J. Biochem. 49, 71.CrossRefGoogle Scholar
Lyman, R. L., Sheehan, G. & Tinoco, J. (1973). Lipids 8, 71.CrossRefGoogle Scholar
Melamed, E. (1979). In Folic Acid in Neurology, Psychiatry, and Internal Medicine, p. 423 [Botez, M. I. and Reynolds, E. H., editors]. New York: Raven Press.Google Scholar
Nesbit, M., Krivit, W., Heyn, R. & Sharp, H. (1976). Cancer 37, 1048.3.0.CO;2-V>CrossRefGoogle Scholar
Ordonez, L. A. & Wurtman, R. J. (1974). Archs Biochem. Biophys. 160, 372.CrossRefGoogle Scholar
Peifer, J. J. & Lewis, R. D. (1979). J. Nutr. 109, 2160.CrossRefGoogle Scholar
Roenigk, H. H., Bergfeld, W. F., Jaques, R. St., Owens, F. J. & Hawk, W. A. (1971). Archs Derm. 103, 250.CrossRefGoogle Scholar
Schneider, W. J. & Vance, D. E. (1978). Eur. J. Biochem. 85, 181.CrossRefGoogle Scholar
Scott, R. B., Kammer, R. B., Burger, W. & Middleton, F. G. (1969). Anns Int. Med. 69, 111.CrossRefGoogle Scholar
Shapiro, H. A., Trowbridge, J. O., Lee, J. C. & Mairbach, H. I. (1974). Archs Derm. 110, 551.CrossRefGoogle Scholar
Shaw, D. M., Macsweeney, D. A., Johnson, A. L., O'Keefe, R., Naidoo, D., MacLeod, D. M., Jog, S., Preece, J. M. & Crowley, J. M. (1971). Psychol. Med. 1, 166.CrossRefGoogle Scholar
Sipos, J. C. & Ackman, R. G. (1978). J. Chrom. Sci. 16, 443.CrossRefGoogle Scholar
Sundler, R. (1973). Biochim. biophys. Acta. 306, 218.CrossRefGoogle Scholar
Sundler, R. (1975). J. biol. Chem. 250, 8585.CrossRefGoogle Scholar
Sundler, R. & Åkesson, B. (1975). J. biol. Chem. 250, 3359.CrossRefGoogle Scholar
Sundler, R., Arvidson, G. & Åkesson, B. (1972). Biochim. Biophys. Acta 280, 559.CrossRefGoogle Scholar
Tokmakjian, S. & Haines, D. S. M. (1979). Can. J. Biochem. 57, 566.CrossRefGoogle Scholar