Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1987 Jan 15;241(2):469–474. doi: 10.1042/bj2410469

Altered interactions between lipogenesis and fatty acid oxidation in regenerating rat liver.

P S Schofield, M C Sugden, C G Corstorphine, V A Zammit
PMCID: PMC1147584  PMID: 3593202

Abstract

The concentrations of malonyl-CoA, citrate, ketone bodies and long-chain acylcarnitine were measured in freeze-clamped liver samples from fed or starved normal, partially hepatectomized or sham-operated rats. These parameters were used in conjunction with measurements of the concentration of plasma non-esterified fatty acids and the rates of hepatic lipogenesis to obtain correlations between rates of fatty acid delivery to the liver, lipogenesis and fatty acid oxidation to ketone bodies and CO2. These correlations indicated that the development of fatty liver after partial hepatectomy is due to an increased partitioning of long-chain acyl-CoA towards acylglycerol synthesis and away from acylcarnitine formation. However, this did not appear to be due to an altered relationship between hepatic malonyl-CoA concentration and acylcarnitine formation. For any concentration of long-chain acylcarnitine, the concentrations of both hepatic and blood ketone bodies were significantly lower in partially hepatectomized rats than in normal or sham-operated animals. This indicated that a lower proportion of the product of beta-oxidation was used for ketone-body formation and more for citrate synthesis in the regenerating liver, especially during the first 24 h after resection. This inference was supported by the changes in hepatic citrate concentrations observed. The high rates of lipogenesis that occurred in the liver remnant were accompanied by an altered relationship between lipogenic rate and hepatic malonyl-CoA concentration, such that much lower concentrations of malonyl-CoA were associated with any given rate of lipogenesis. These adaptations are discussed in relation to the requirements by the remnant for high rates of energy formation through the tricarboxylic acid cycle during the first 24 h after resection, and the possibility that cycling between fatty acid oxidation and synthesis may occur to a greater degree in regenerating liver.

Full text

PDF
469

Selected References

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

  1. BRAUER R. W. Liver circulation and function. Physiol Rev. 1963 Jan;43:115–213. doi: 10.1152/physrev.1963.43.1.115. [DOI] [PubMed] [Google Scholar]
  2. Beynen A. C., Vaartjes W. J., Geelen M. J. Opposite effects of insulin and glucagon in acute hormonal control of hepatic lipogenesis. Diabetes. 1979 Sep;28(9):828–835. doi: 10.2337/diab.28.9.828. [DOI] [PubMed] [Google Scholar]
  3. Blackshear P. J., Holloway P. A., Alberti K. G. The metabolic effects of sodium dichloroacetate in the starved rat. Biochem J. 1974 Aug;142(2):279–286. doi: 10.1042/bj1420279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cederblad G., Lindstedt S. A method for the determination of carnitine in the picomole range. Clin Chim Acta. 1972 Mar;37:235–243. doi: 10.1016/0009-8981(72)90438-x. [DOI] [PubMed] [Google Scholar]
  5. Christiansen R., Borrebaek B., Bremer J. The effect of (-)carnitine on the metabolism of palmitate in liver cells isolated from fasted and refed rats. FEBS Lett. 1976 Mar 1;62(3):313–317. doi: 10.1016/0014-5793(76)80083-x. [DOI] [PubMed] [Google Scholar]
  6. Fex G., Olivecrona T. The metabolism of [3H]oleic acid in the partially hepatectomized rat. Biochim Biophys Acta. 1968 Mar 4;152(2):237–243. doi: 10.1016/0005-2760(68)90032-5. [DOI] [PubMed] [Google Scholar]
  7. Field F. J., Mathur S. N., LaBrecque D. R. Cholesterol metabolism in regenerating liver of the rat. Am J Physiol. 1985 Dec;249(6 Pt 1):G679–G684. doi: 10.1152/ajpgi.1985.249.6.G679. [DOI] [PubMed] [Google Scholar]
  8. Girard A., Roheim P. S., Eder H. A. Lipoprotein synthesis and fatty acid mobilization in rats after partial hepatectomy. Biochim Biophys Acta. 1971 Oct 5;248(1):105–113. doi: 10.1016/0005-2760(71)90080-4. [DOI] [PubMed] [Google Scholar]
  9. Gove C. D., Hems D. A. Fatty acid synthesis in the regenerating liver of the rat. Biochem J. 1978 Jan 15;170(1):1–8. doi: 10.1042/bj1700001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Guynn R. W., Veloso D., Veech R. L. The concentration of malonyl-coenzyme A and the control of fatty acid synthesis in vivo. J Biol Chem. 1972 Nov 25;247(22):7325–7331. [PubMed] [Google Scholar]
  11. JOHNSON R. M., ALBERT S. Glycerol- and acetate-C14 incorporation into lipids of tissues undergoing cell division. J Biol Chem. 1960 May;235:1299–1302. [PubMed] [Google Scholar]
  12. Krebs H. A. The regulation of the release of ketone bodies by the liver. Adv Enzyme Regul. 1966;4:339–354. doi: 10.1016/0065-2571(66)90027-6. [DOI] [PubMed] [Google Scholar]
  13. Mangiapane E. H., Lloyd-Davies K. A., Brindley D. N. A study of some enzymes of glycerolipid biosynthesis in rat liver after subtotal hepatectomy. Biochem J. 1973 May;134(1):103–112. doi: 10.1042/bj1340103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Olivecrona T., Fex G. Metabolism of plasma lipids in partially hepatectomized rats. Biochim Biophys Acta. 1970 Mar 10;202(2):259–268. doi: 10.1016/0005-2760(70)90187-6. [DOI] [PubMed] [Google Scholar]
  15. Schofield P. S., French T. J., Goode A. W., Sugden M. C. Liver carnitine metabolism after partial hepatectomy in the rat. Effects of nutritional status and inhibition of carnitine palmitoyltransferase. FEBS Lett. 1985 May 20;184(2):214–220. doi: 10.1016/0014-5793(85)80609-8. [DOI] [PubMed] [Google Scholar]
  16. Schofield P. S., McLees D. J., Myles D. D., Sugden M. C. Ketone-body metabolism after partial hepatectomy in the rat. Biochem J. 1985 Oct 1;231(1):225–228. doi: 10.1042/bj2310225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Siess E. A., Kientsch-Engel R. I., Wieland O. H. Role of free oxaloacetate in ketogenesis. Derivation from the direct measurement of mitochondrial [3-hydroxybutyrate]/[acetoacetate] ratio in hepatocytes. Eur J Biochem. 1982 Jan;121(3):493–499. doi: 10.1111/j.1432-1033.1982.tb05814.x. [DOI] [PubMed] [Google Scholar]
  18. Stansbie D., Brownsey R. W., Crettaz M., Denton R. M. Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Biochem J. 1976 Nov 15;160(2):413–416. doi: 10.1042/bj1600413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zammit V. A. Mechanisms of regulation of the partition of fatty acids between oxidation and esterification in the liver. Prog Lipid Res. 1984;23(1):39–67. doi: 10.1016/0163-7827(84)90005-5. [DOI] [PubMed] [Google Scholar]
  21. Zammit V. A. Regulation of hepatic fatty acid metabolism. The activities of mitochondrial and microsomal acyl-CoA:sn-glycerol 3-phosphate O-acyltransferase and the concentrations of malonyl-CoA, non-esterified and esterified carnitine, glycerol 3-phosphate, ketone bodies and long-chain acyl-CoA esters in livers of fed or starved pregnant, lactating and weaned rats. Biochem J. 1981 Jul 15;198(1):75–83. doi: 10.1042/bj1980075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zammit V. A. Regulation of hepatic fatty acid oxidation and ketogenesis. Proc Nutr Soc. 1983 Jun;42(2):289–302. doi: 10.1079/pns19830033. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES