Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1982 May 15;204(2):433–439. doi: 10.1042/bj2040433

Insulin and non-esterified fatty acids. Acute regulators of lipogenesis in perfused rat liver.

D L Topping, P A Mayes
PMCID: PMC1158369  PMID: 7052069

Abstract

Livers from fed rats were perfused with whole rat blood and infused with oleate to maintain constant concentrations of serum non-esterified fatty acids over a wide physiological range. Infusion of insulin opposed the antilipogenic effects of increasing concentrations of serum non-esterified fatty acids. Secretion of very-low-density-lipoprotein triacylglycerols was directly proportional to the concentration of serum non-esterified fatty acids and was increased by insulin. The secretion of newly-synthesized fatty acids in very-low-density-lipoprotein triacylglycerols decreased with increasing concentrations of serum non-esterified fatty acid. Insulin opposed this change. Cholesterol biosynthesis was unaffected by alterations in concentration of serum non-esterified fatty acid but was increased by insulin. Equilibrium concentrations of perfusate lactate and glucose were increased by serum non-esterified fatty acids but steady-state rates of hepatic glucose output and lactate uptake were unchanged. Insulin decreased perfusate glucose concentrations and abolished the increase in its concentration that resulted from increases in non-esterified fatty acid concentrations.

Full text

PDF

Selected References

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

  1. BORTZ W. M., LYNEN F. THE INHIBITION OF ACETYL COA CARBOXYLASE BY LONG CHAIN ACYL COA DERIVATIVES. Biochem Z. 1963 Aug 14;337:505–509. [PubMed] [Google Scholar]
  2. Bates E. J., Topping D. L., Sooranna S. P., Saggerson D., Mayes P. A. Acute effects of insulin on glycerol phosphate acyl transferase activity, ketogenesis and serum free fatty acid concentration in perfused rat liver. FEBS Lett. 1977 Dec 15;84(2):225–228. doi: 10.1016/0014-5793(77)80693-5. [DOI] [PubMed] [Google Scholar]
  3. Bricker L. A., Levey G. S. Evidence for regulatin of cholesterol and fatty acid synthesis in liver by cyclic adenosine 3',5'-monophosphate. J Biol Chem. 1972 Aug 10;247(15):4914–4915. [PubMed] [Google Scholar]
  4. Capuzzi D. M., Rothman V., Margolis S. The regulation of lipogenesis by cyclic nucleotides in intact hepatocytes prepared by a simplified technique. J Biol Chem. 1974 Feb 25;249(4):1286–1294. [PubMed] [Google Scholar]
  5. Clark D. G., Rognstad R., Katz J. Lipogenesis in rat hepatocytes. J Biol Chem. 1974 Apr 10;249(7):2028–2036. [PubMed] [Google Scholar]
  6. Exton J. H., Corbin J. G., Harper S. C. Control of gluconeogenesis in liver. V. Effects of fasting, diabetes, and glucagon on lactate and endogenous metabolism in the perfused rat liver. J Biol Chem. 1972 Aug 25;247(16):4996–5003. [PubMed] [Google Scholar]
  7. Exton J. H. Mechanisms involved in alpha-adrenergic effects of catecholamines on liver metabolism. J Cyclic Nucleotide Res. 1979;5(4):277–287. [PubMed] [Google Scholar]
  8. Exton J. H., Park C. R. Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats. J Biol Chem. 1967 Jun 10;242(11):2622–2636. [PubMed] [Google Scholar]
  9. Geelen M. J., Beynen A. C., Christiansen R. Z., Lepreau-Jose M. J., Gibson D. M. Short-term effects of insulin and glucagon on lipid synthesis in isolated rat hepatocytes. Covariance of acetyl-CoA carboxylase activity and the rate of 3H2O incorporation into fatty acids. FEBS Lett. 1978 Nov 15;95(2):326–330. doi: 10.1016/0014-5793(78)81022-9. [DOI] [PubMed] [Google Scholar]
  10. Goh E. H., Heimberg M. Effect of oleic acid and cholesterol on the activity of hepatic hydroxymethylglutaryl coenzyme A reductase. FEBS Lett. 1976 Mar 15;63(1):209–210. doi: 10.1016/0014-5793(76)80228-1. [DOI] [PubMed] [Google Scholar]
  11. Halperin M. L., Robinson B. H., Fritz I. B. Effects of palmitoyl CoA on citrate and malate transport by rat liver mitochondria. Proc Natl Acad Sci U S A. 1972 Apr;69(4):1003–1007. doi: 10.1073/pnas.69.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hems D. A. Rapid hormonal control of hepatic catabolism in health and disease. Clin Sci (Lond) 1979 Mar;56(3):197–202. doi: 10.1042/cs0560197. [DOI] [PubMed] [Google Scholar]
  13. Keith M. L., Rodwell V. W., Rogers D. H., Rudney H. In vitro phosphorylation of 3-hydroxy-3-methylglutaryl coenzyme A reductase: analysis of 32P-labeled, inactivated enzyme. Biochem Biophys Res Commun. 1979 Oct 12;90(3):969–975. doi: 10.1016/0006-291x(79)91922-3. [DOI] [PubMed] [Google Scholar]
  14. Lakshmanan M. R., Nepokroeff C. M., Ness G. C., Dugan R. E., Porter J. W. Stimulation by insulin of rat liver -hydroxy- -methylglutaryl coenzyme A reductase and cholesterol-synthesizing activities. Biochem Biophys Res Commun. 1973 Feb 5;50(3):704–710. doi: 10.1016/0006-291x(73)91301-6. [DOI] [PubMed] [Google Scholar]
  15. Mayes P. A., Topping D. L. Regulation of hepatic lipogenesis by plasma free fatty acids: simultaneous studies on lipoprotein secretion, cholesterol synthesis, ketogenesis and gluconeogenesis. Biochem J. 1974 Apr;140(1):111–114. doi: 10.1042/bj1400111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nepokroeff C. M., Lakshmanan M. R., Ness G. C., Dugan R. E., Porter J. W. Regulation of the diurnal rhythm of rat liver beta-hydroxy-beta-methylglutaryl coenzmye A reductase activity by insulin, glucagon, cyclic AMP and hydrocortisone. Arch Biochem Biophys. 1974 Feb;160(2):387–396. doi: 10.1016/0003-9861(74)90412-3. [DOI] [PubMed] [Google Scholar]
  17. Salmon D. M., Bowen N. L., Hems D. A. Synthesis of fatty acids in the perused mouse liver. Biochem J. 1974 Sep;142(3):611–618. doi: 10.1042/bj1420611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Salmon D. M., Hems D. A. A direct effect of insulin on fatty acid monodesaturation in the perfused mouse liver. Biochem Soc Trans. 1975;3(4):510–512. doi: 10.1042/bst0030510. [DOI] [PubMed] [Google Scholar]
  19. Siess E. A., Wieland O. H. Phosphorylation state of cytosolic and mitochondrial adenine nucleotides and of pyruvate dehydrogenase in isolated rat liver cells. Biochem J. 1976 Apr 15;156(1):91–102. doi: 10.1042/bj1560091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Storer G. B., Topping D. L., Trimble R. P. Direct stimulation by glucose and insulin of glycogen synthesis in perfused rat liver. FEBS Lett. 1981 Dec 21;136(1):135–137. doi: 10.1016/0014-5793(81)81231-8. [DOI] [PubMed] [Google Scholar]
  21. Storer G. B., Trimble R. P., Topping D. L. Impaired sensitivity to insulin of rat livers perfused with blood of diminished haematocrit. Biochem J. 1980 Oct 15;192(1):219–222. doi: 10.1042/bj1920219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. TROUT D. L., ESTES E. H., Jr, FRIEDBERG S. J. Titration of free fatty acids of plasma: a study of current methods and a new modification. J Lipid Res. 1960 Apr;1:199–202. [PubMed] [Google Scholar]
  23. Topping D. L., Clark D. G., Storer G. B., Trimble R. P., Illman R. J. Acute effects of ethanol on the perfused rat liver. Studies on lipid and carbohydrate metabolism, substrate cycling and perfusate amino acids. Biochem J. 1979 Oct 15;184(1):97–106. doi: 10.1042/bj1840097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Topping D. L., Mayes F. A. Regulation of lipogenesis by insulin and free fatty acids in perfused rat liver. Biochem Soc Trans. 1976;4(4):717–717. doi: 10.1042/bst0040717. [DOI] [PubMed] [Google Scholar]
  25. Topping D. L., Mayes P. A. Comparative effects of fructose and glucose on the lipid and carbohydrate metabolism of perfused rat liver. Br J Nutr. 1976 Jul;36(1):113–126. doi: 10.1079/bjn19760062. [DOI] [PubMed] [Google Scholar]
  26. Topping D. L., Mayes P. A. The concentration of fructose, glucose and lactate in the splanchnic blood vessels of rats absorbing fructose. Nutr Metab. 1971;13(6):331–338. doi: 10.1159/000175352. [DOI] [PubMed] [Google Scholar]
  27. Topping D. L., Mayes P. A. The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohydrate metabolism. Biochem J. 1972 Jan;126(2):295–311. doi: 10.1042/bj1260295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wieland O. H., Patzelt C., Löffler G. Active and inactive forms of pyruvate dehydrogenase in rat liver. Effect of starvation and refeeding and of insulin treatment on pyruvate-dehydrogenase interconversion. Eur J Biochem. 1972 Apr 11;26(3):426–433. doi: 10.1111/j.1432-1033.1972.tb01783.x. [DOI] [PubMed] [Google Scholar]
  29. Williamson J. R., Kreisberg R. A., Felts P. W. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A. 1966 Jul;56(1):247–254. doi: 10.1073/pnas.56.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Windmueller H. G., Spaeth A. E. De novo synthesis of fatty acid in perfused rat liver as a determinant of plasma lipoprotein production. Arch Biochem Biophys. 1967 Nov;122(2):362–369. doi: 10.1016/0003-9861(67)90206-8. [DOI] [PubMed] [Google Scholar]
  31. Windmueller H. G., Spaeth A. E. Perfusion in situ with tritium oxide to measure hepatic lipogenesis and lipid secretion. Normal and orotic acid-fed rats. J Biol Chem. 1966 Jun 25;241(12):2891–2899. [PubMed] [Google Scholar]
  32. Witters L. A., Moriarity D., Martin D. B. Regulation of hepatic acetyl coenzyme A carboxylase by insulin and glucagon. J Biol Chem. 1979 Jul 25;254(14):6644–6649. [PubMed] [Google Scholar]

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

RESOURCES