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. 1978 Dec 15;176(3):777–784. doi: 10.1042/bj1760777

The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver

Helen P Glenny 1, David N Brindley 1
PMCID: PMC1186300  PMID: 218553

Abstract

1. Male rats were injected daily for 5 days with 0.15m-NaCl, corticotropin, cortisol or l-thyroxine and the rates of glycerolipid synthesis were measured in the livers after intraportal injection of [14C]palmitate and [3H]glycerol. 2. Injection of all three hormones decreased the rates of body-weight gain. 3. Cortisol treatment increased the weight of the liver relative to body weight. 4. Thyroxine treatment increased the relative rate of triacylglycerol synthesis from [3H]glycerol and decreased the relative accumulation of 3H and 14C in diacylglycerol. It did not significantly alter the accumulation of these isotopes in phosphatidate nor the activity of the soluble phosphatidate phosphohydrolase in the total liver. However, this activity increased by 1.5-fold when expressed relative to the soluble protein of the liver. The increased triacylglycerol synthesis appears to be related to a general increase in the turnover of fatty acids in the liver. 5. Treatment with cortisol and corticotropin increased the relative rate of triacylglycerol synthesis from [3H]glycerol, decreased the accumulation of 3H in phosphatidate and increased the flux of both isotopes from phosphatidate to diacylglycerol. This appeared to be caused by the increased activity of the soluble phosphatidate phosphohydrolase that was observed in the livers of the cortisol-treated rats. 6. It is proposed that cortisol could be directly or indirectly involved in increasing the activity of hepatic phosphatidate phosphohydrolase in starvation, diabetes, laparotomy, subtotal hepatectomy, liver damage, ethanol feeding and in obesity. This enzyme adaptation could contribute to the potential of the liver to increase its synthesis and accumulation of triacylglycerols or to secrete very-low-density lipoproteins.

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Selected References

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  1. Bates R. W., Garrison M. M. Hormonal interactions among GH, ACTH, cortisol and dexamethasone upon size of kidney, liver, and adrenal. Proc Soc Exp Biol Med. 1974 Jul;146(3):725–731. doi: 10.3181/00379727-146-38181. [DOI] [PubMed] [Google Scholar]
  2. Bizzi A., Tacconi A. M., Garattini S. Relationship between lipolysis and storage of corticosterone in adipose tissue. Biochem Pharmacol. 1972 Apr 1;21(7):999–1008. doi: 10.1016/0006-2952(72)90404-2. [DOI] [PubMed] [Google Scholar]
  3. Bressler R., Wittels B. The effect of thyroxine on lipid and carbohdrate metabolism in the heart. J Clin Invest. 1966 Aug;45(8):1326–1333. doi: 10.1172/JCI105439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brindley D. N., Bowley M., Burditt S., Pritchard H., Lloyd-Davies K. A., Boucrot P. The effects of administering N-(2-benzoyloxyethyl) norfenfluramine to rats on the hepatic synthesis of glycerolipids. J Pharm Pharmacol. 1976 Sep;28(9):676–682. doi: 10.1111/j.2042-7158.1976.tb02835.x. [DOI] [PubMed] [Google Scholar]
  5. Brindley D. N. Some aspects of the physiological and pharmacological control of the synthesis of triacylglycerols and phospholipids. Int J Obes. 1978;2(1):7–16. [PubMed] [Google Scholar]
  6. Chernick S. S., Clark C. M., Jr, Gardiner R. J., Scow R. O. Role of lipolytic and glucocorticoid hormones in the development of diabetic ketosis. Diabetes. 1972 Sep;21(9):946–954. doi: 10.2337/diab.21.9.946. [DOI] [PubMed] [Google Scholar]
  7. Coates P. M., Brown S. A., Lau H., Krulich L., Koldovsky O. Effect of thyroxine on acid lipase activity of adult rat liver. FEBS Lett. 1978 Feb 1;86(1):45–48. doi: 10.1016/0014-5793(78)80095-7. [DOI] [PubMed] [Google Scholar]
  8. Diamant S., Gorin E., Shafrir E. Enzyme activities related to fatty-acid synthesis in liver and adipose tissue of rats treated with triiodothyronine. Eur J Biochem. 1972 Apr 24;26(4):553–559. doi: 10.1111/j.1432-1033.1972.tb01798.x. [DOI] [PubMed] [Google Scholar]
  9. Diamant S., Shafrir E. Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids. Eur J Biochem. 1975 May 6;53(2):541–546. doi: 10.1111/j.1432-1033.1975.tb04097.x. [DOI] [PubMed] [Google Scholar]
  10. Fallon H. J., Lamb R. G., Jamdar S. C. Phosphatidate phosphohydrolase and the regulation of glycerolipid biosynthesis. Biochem Soc Trans. 1977;5(1):37–40. doi: 10.1042/bst0050037. [DOI] [PubMed] [Google Scholar]
  11. Gibson D. M., Lyons R. T., Scott D. F., Muto Y. Synthesis and degradation of the lipogenic enzymes of rat liver. Adv Enzyme Regul. 1972;10:187–204. doi: 10.1016/0065-2571(72)90014-3. [DOI] [PubMed] [Google Scholar]
  12. Glenny H. P., Bowley M., Burditt S. L., Cooling J., Pritchard P. H., Sturton R. G., Brindley D. N. The effect of dietary carbohydrate and fat on the activities of some enzymes responsible for glycerolipid synthesis in rat liver. Biochem J. 1978 Aug 15;174(2):535–541. doi: 10.1042/bj1740535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HILL R. B., Jr, DROKE W. A. PRODUCTION OF FATTY LIVER IN THE RAT BY CORTISONE. Proc Soc Exp Biol Med. 1963 Dec;114:766–769. doi: 10.3181/00379727-114-28790. [DOI] [PubMed] [Google Scholar]
  14. Herberg L., Coleman D. L. Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism. 1977 Jan;26(1):59–99. doi: 10.1016/0026-0495(77)90128-7. [DOI] [PubMed] [Google Scholar]
  15. Jamdar S. C., Shapiro D., Fallon H. J. Triacylglycerol biosynthesis in the adipose tissue of the obese-hyperglycaemic mouse. Biochem J. 1976 Aug 15;158(2):327–334. doi: 10.1042/bj1580327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Johnston J. M., Schultz M., Jimenez J. M., MacDonald P. C. Phospholipid biosynthesis: the activity of phosphatidic acid phosphohydrolase in the developing lung and amnionic fluid. Chest. 1975 Feb;67(2 Suppl):18S–21S. doi: 10.1378/chest.67.2.18s. [DOI] [PubMed] [Google Scholar]
  17. Kako K. J., Patterson S. D. Phosphatidate phosphohydrolase and palmitoyl-coenzyme A hydrolase in cardiac subcellular fractions of hyperthyroid rabbits and cardiomyopathic hamsters. Biochem J. 1975 Nov;152(2):313–323. doi: 10.1042/bj1520313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kirk C. J., Verrinder T. R., Hems D. A. Fatty acid synthesis in the perfused liver of adrenalectomized rats. Biochem J. 1976 Jun 15;156(3):593–602. doi: 10.1042/bj1560593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klausner H., Heimberg M. Effect of adrenalcortical hormones on release of triglycerides and glucose by liver. Am J Physiol. 1967 Jun;212(6):1236–1246. doi: 10.1152/ajplegacy.1967.212.6.1236. [DOI] [PubMed] [Google Scholar]
  20. Lebovitz H. E., Bryant K., Frohman L. A. Acute effects of corticotropin and related peptides on carbohydrate and lipid metabolism. Ann N Y Acad Sci. 1965 Oct 8;131(1):274–287. doi: 10.1111/j.1749-6632.1965.tb34796.x. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Nikkilä E. A., Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest. 1972 Aug;51(8):2103–2114. doi: 10.1172/JCI107017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ozegović B., Rodè B., Milkivić S. The role of the adrenal gland in the lipid accumulation process in the liver of rats bearing an acth and prolactin producing tumor. Endokrinologie. 1975 Nov;66(2):128–134. [PubMed] [Google Scholar]
  24. Possmayer F., Duwe G., Metcalfe R., Stewart-DeHaan P. J., Wong C., Heras J. L., Harding P. G. Cortisol induction of pulmonary maturation in the rabbit foetus. Its effects on enzymes related to phospholipid biosynthesis and on marker enzymes for subcellular organelles. Biochem J. 1977 Sep 15;166(3):485–494. doi: 10.1042/bj1660485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pritchard P. H., Bowley M., Burditt S. L., Cooling J., Glenny H. P., Lawson N., Sturton R. G., Brindley D. N. The effects of acute ethanol feeding and of chronic benfluorex administration on the activities of some enzymes of glycerolipid synthesis in rat liver and adipose tissue. Biochem J. 1977 Sep 15;166(3):639–642. doi: 10.1042/bj1660639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pritchard P. H., Brindley D. N. Studies on the ethanol-induced changes in glycerolipid synthesis in rats and their partial reversal by N-(2-benzoyloxyethyl)norfenfluramine (benfluorex). J Pharm Pharmacol. 1977 Jun;29(6):343–349. doi: 10.1111/j.2042-7158.1977.tb11332.x. [DOI] [PubMed] [Google Scholar]
  27. RAMEY E. R., GOLDSTEIN M. S. The adrenal cortex and the sympathetic nervous system. Physiol Rev. 1957 Apr;37(2):155–195. doi: 10.1152/physrev.1957.37.2.155. [DOI] [PubMed] [Google Scholar]
  28. Reaven E. P., Kolterman O. G., Reaven G. M. Ultrastructural and physiological evidence for corticosteroid-induced alterations in hepatic production of very low density lipoprotein particles. J Lipid Res. 1974 Jan;15(1):74–83. [PubMed] [Google Scholar]
  29. Roncari D. A., Murthy V. K. Effects of thyroid hormones on enzymes involved in fatty acid and glycerolipid synthesis. J Biol Chem. 1975 Jun 10;250(11):4134–4138. [PubMed] [Google Scholar]
  30. Salmon D. M., Hems D. A. Plasma lipoproteins and the synthesis and turnover of plasma triglyceride in normal and genetically obese mice. Biochem J. 1973 Nov;136(3):551–563. doi: 10.1042/bj1360551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Savolainen M. J. Stimulation of hepatic phosphatidate phosphohydrolase activity by a single dose of ethanol;. Biochem Biophys Res Commun. 1977 Mar 21;75(2):511–518. doi: 10.1016/0006-291x(77)91071-3. [DOI] [PubMed] [Google Scholar]
  32. Scow R. O., Stricker F. A., Pick T. Y., Clary T. R. Effect of ACTH on FFA release and diglyceride content in perfused rat adipose tissue. Ann N Y Acad Sci. 1965 Oct 8;131(1):288–301. doi: 10.1111/j.1749-6632.1965.tb34797.x. [DOI] [PubMed] [Google Scholar]
  33. Sturton R. G., Brindley D. N. Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. The effects of chlorpromazine, demethylimipramine, cinchocaine, norfenfluramine, mepyramine and magnesium ions. Biochem J. 1977 Jan 15;162(1):25–32. doi: 10.1042/bj1620025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sturton R. G., Brindley D. N. Problems encountered in measuring the activity of phosphatidate phosphohydrolase. Biochem J. 1978 Apr 1;171(1):263–266. doi: 10.1042/bj1710263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sturton R. G., Pritchard P. H., Han L. Y., Brindley D. N. The involvement of phosphatidate phosphohydrolase and phospholipase A activities in the control of hepatic glycerolipid synthesis. Effects of acute feeding with glucose, fructose, sorbitol, glycerol and ethanol. Biochem J. 1978 Aug 15;174(2):667–670. doi: 10.1042/bj1740667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Szabo S., Kourounakis P., Selye H. Effect of adrenocorticotropin (ACTH) upon the drug response of intact and adrenalectomized rats. Can J Physiol Pharmacol. 1973 Mar;51(3):169–174. doi: 10.1139/y73-024. [DOI] [PubMed] [Google Scholar]
  37. TEPPERMAN H. M., TEPPERMAN J. PATTERNS OF DIETARY AND HORMONAL INDUCTION OF CERTAIN NADP-LINKED LIVER ENZYMES. Am J Physiol. 1964 Feb;206:357–361. doi: 10.1152/ajplegacy.1964.206.2.357. [DOI] [PubMed] [Google Scholar]
  38. Tulloch B. R., Lewis B., Fraser T. R. Triglyceride metabolism in thyroid disease. Lancet. 1973 Feb 24;1(7800):391–394. doi: 10.1016/s0140-6736(73)90250-x. [DOI] [PubMed] [Google Scholar]
  39. Vavrecka M., Mitchell M. P., Hübscher G. The effect of starvation on the incorporation of palmitate into glycerides and phospholipids of rat liver homogenates. Biochem J. 1969 Nov;115(2):139–145. doi: 10.1042/bj1150139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. WEBER G., SINGHAL R. L. ROLE OF ENZYMES IN HOMEOSTASIS. V. ACTINOMYCIN AND PUROMYCIN INHIBITION OF CORTISONE-INDUCED SYNTHESIS OF HEPATIC GLUCOSE 6-PHOSPHATASE AND FRUCTOSE 1,6-DIPHOSPHATASE. J Biol Chem. 1964 Feb;239:521–526. [PubMed] [Google Scholar]
  41. Walter P., Anabitarte M. Intracellular distribution of pyruvate carboxylase in livers of normal and cortisol treated rats. FEBS Lett. 1973 Dec 1;37(2):170–173. doi: 10.1016/0014-5793(73)80451-x. [DOI] [PubMed] [Google Scholar]
  42. Whiting P. H., Bowley M., Sturton R. G., Pritchard P. H., Brindley D. N., Hawthorne J. N. The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver. Biochem J. 1977 Nov 15;168(2):147–153. doi: 10.1042/bj1680147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Young D. L., Lynen F. Enzymatic regulation of 3-sn-phosphatidylcholine and triacylglycerol synthesis in states of altered lipid metabolism. J Biol Chem. 1969 Jan 25;244(2):377–383. [PubMed] [Google Scholar]

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