Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 Mar 15;210(3):937–944. doi: 10.1042/bj2100937

Interactions between insulin and thyroid hormone in the control of lipogenesis.

M C Sugden, S E Steare, D I Watts, T N Palmer
PMCID: PMC1154310  PMID: 6135416

Abstract

1. The effects of intragastric glucose feeding and L-tri-iodothyronine (T3) administration on rates of hepatic and brown-fat lipogenesis in vivo were examined in fed and 48 h-starved rats. 2. T3 treatment increased hepatic lipogenesis in the fed but not the starved animals. Brown-fat lipogenesis was unaffected or slightly decreased by T3 treatment of fed or starved rats. 3. Intragastric glucose feeding increased hepatic lipogenesis in control or T3-treated fed rats, but did not increase hepatic lipogenesis in starved control rats. Glucose feeding increased hepatic lipogenesis if the starved rats were treated with T3. Glucose feeding increased rates of brown-fat lipogenesis in all experimental groups. The effects of glucose feeding on liver and brown-fat lipogenesis were mimicked by insulin injection. 4. The increase in hepatic lipogenesis in T3-treated 48 h-starved rats after intragastric glucose feeding was prevented by short-term insulin deficiency, but not by (-)-hydroxycitrate, an inhibitor of ATP citrate lyase. The increase in lipogenesis in brown adipose tissue in response to glucose feeding was inhibited by both short-term insulin deficiency and (-)-hydroxycitrate. 5. The results tend to preclude pyruvate kinase and acetyl-CoA carboxylase as the sites of interaction of insulin and T3 in the regulation of hepatic lipogenesis in 48 h-starved rats. Other potential sites of interaction are discussed.

Full text

PDF
937

Selected References

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

  1. ALLMANN D. W., HUBBARD D. D., GIBSON D. M. FATTY ACID SYNTHESIS DURING FAT-FREE REFEEDING OF STARVED RATS. J Lipid Res. 1965 Jan;6:63–74. [PubMed] [Google Scholar]
  2. Agius L., Williamson D. H. Lipogenesis in interscapular brown adipose tissue of virgin, pregnant and lactating rats. The effects of intragastric feeding. Biochem J. 1980 Aug 15;190(2):477–480. doi: 10.1042/bj1900477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agius L., Williamson D. H. The utilization of ketone bodies by the interscapular brown adipose tissue of the rat. Biochim Biophys Acta. 1981 Oct 23;666(1):127–132. doi: 10.1016/0005-2760(81)90098-9. [DOI] [PubMed] [Google Scholar]
  4. Baquer N. Z., Cascales M., McLean P., Greenbaum A. L. Effects of thyroid hormone deficiency on the distribution of hepatic metabolites and control of pathways of carbohydrate metabolism in liver and adipose tissue of the rat. Eur J Biochem. 1976 Sep 15;68(2):403–413. doi: 10.1111/j.1432-1033.1976.tb10827.x. [DOI] [PubMed] [Google Scholar]
  5. Das D. K. Regulation of hepatic fatty acid-synthesizing enzymes of diabetic animals by thyroid-hormone. Arch Biochem Biophys. 1980 Aug;203(1):25–36. doi: 10.1016/0003-9861(80)90150-2. [DOI] [PubMed] [Google Scholar]
  6. Davies D. R., Van Schaftingen E., Hers H. G. Interference by pyruvate carboxylase in the measurement of acetyl-CoA carboxylase in crude liver preparations. Biochem J. 1982 Feb 15;202(2):559–560. doi: 10.1042/bj2020559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Feliú J. E., Hue L., Hers H. G. Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2762–2766. doi: 10.1073/pnas.73.8.2762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Felíu J. E., Hue L., Hers H. G. Regulation in vitro and in vivo of adenosine 3':5'-monophosphate-dependent inactivation of rat-liver pyruvate kinase type L. Eur J Biochem. 1977 Dec;81(3):609–617. doi: 10.1111/j.1432-1033.1977.tb11988.x. [DOI] [PubMed] [Google Scholar]
  10. Gnoni G. V., Landriscina C., Quagliariello E. Fatty acid biosynthesis in adipose tissue and lung subcellular fractions of thyrotoxic rats. FEBS Lett. 1980 Dec 15;122(1):37–40. doi: 10.1016/0014-5793(80)80396-6. [DOI] [PubMed] [Google Scholar]
  11. Goodman H. M., Bray G. A. Role of thyroid hormones in lipolysis. Am J Physiol. 1966 May;210(5):1053–1058. doi: 10.1152/ajplegacy.1966.210.5.1053. [DOI] [PubMed] [Google Scholar]
  12. Halestrap A. P., Denton R. M. Hormonal regulation of adipose-tissue acetyl-Coenzyme A carboxylase by changes in the polymeric state of the enzyme. The role of long-chain fatty acyl-Coenzyme A thioesters and citrate. Biochem J. 1974 Aug;142(2):365–377. doi: 10.1042/bj1420365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hems D. A., Whitton P. D., Taylor E. A. Glycogen synthesis in the perfused liver of the starved rat. Biochem J. 1972 Sep;129(3):529–538. doi: 10.1042/bj1290529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hopkirk T. J., Bloxham D. P. Studies on the biosynthesis of hepatic pyruvate kinase and its correlation with enhanced hepatic lipogenesis in meal-trained rats. Biochem J. 1979 Aug 15;182(2):383–397. doi: 10.1042/bj1820383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hopkirk T. J., Bloxham D. Fatty acid synthesis and metabolite fluctuations in meal-fed rats [proceedings]. Biochem Soc Trans. 1977;5(5):1294–1297. doi: 10.1042/bst0051294. [DOI] [PubMed] [Google Scholar]
  16. Lane M. D., Moss J., Polakis S. E. Acetyl coenzyme A carboxylase. Curr Top Cell Regul. 1974;8(0):139–195. [PubMed] [Google Scholar]
  17. McCormack J. G., Denton R. M. Evidence that fatty acid synthesis in the interscapular brown adipose tissue of cold-adapted rats is increased in vivo by insulin by mechanisms involving parallel activation of pyruvate dehydrogenase and acetyl-coenzyme A carboxylase. Biochem J. 1977 Sep 15;166(3):627–630. doi: 10.1042/bj1660627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Munday M. R., Williamson D. H. Effects of starvation, insulin or prolactin deficiency on the activity of acetyl-CoA carboxylase in mammary gland and liver of lactating rats. FEBS Lett. 1982 Feb 22;138(2):285–288. doi: 10.1016/0014-5793(82)80462-6. [DOI] [PubMed] [Google Scholar]
  19. Murthy V. K., Steiner G. Hepatic acetate levels in relation to altered lipid metabolism. Metabolism. 1973 Jan;22(1):81–84. doi: 10.1016/0026-0495(73)90032-2. [DOI] [PubMed] [Google Scholar]
  20. Muto Y., Gibson D. M. Selective dampening of lipogenic enzymes of liver by exogenous polyunsaturated fatty acids. Biochem Biophys Res Commun. 1970 Jan 6;38(1):9–15. doi: 10.1016/0006-291x(70)91076-4. [DOI] [PubMed] [Google Scholar]
  21. Nicholls D. G. Brown adipose tissue mitochondria. Biochim Biophys Acta. 1979 Jul 3;549(1):1–29. doi: 10.1016/0304-4173(79)90016-8. [DOI] [PubMed] [Google Scholar]
  22. Okajima F., Ui M. Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose. Biochem J. 1979 Aug 15;182(2):565–575. doi: 10.1042/bj1820565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oppenheimer J. H., Silva E., Schwartz H. L., Surks M. I. Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated. J Clin Invest. 1977 Mar;59(3):517–527. doi: 10.1172/JCI108667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rognstad R., Katz J. Effects of 2,4-dihydroxybutyrate on lipogenesis in rat hepatocytes. J Biol Chem. 1979 Dec 10;254(23):11969–11972. [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Schein P. S., Alberti K. G., Williamson D. H. Effects of streptozotocin on carbohydrate and lipid metabolism in the rat. Endocrinology. 1971 Sep;89(3):827–834. doi: 10.1210/endo-89-3-827. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Sugden M. C., Watts D. I., Marshall C. E. Effects of adrenaline on ketogenesis from long- and medium-chain fatty acids in starved rats. Biochem J. 1982 Jun 15;204(3):749–756. doi: 10.1042/bj2040749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sugden M. C., Watts D. I., Marshall C. E., McCormack J. G. Brown-adipose-tissue lipogenesis in starvation: effects of insulin and (-) hydroxycitrate. Biosci Rep. 1982 May;2(5):289–297. doi: 10.1007/BF01115114. [DOI] [PubMed] [Google Scholar]
  31. Sugden M. C., Watts D. I., Marshall C. E. Regulation of hepatic lipogenesis in starved and diabetic animals by thyroid hormone. Biosci Rep. 1981 Oct;1(10):757–764. doi: 10.1007/BF01114797. [DOI] [PubMed] [Google Scholar]
  32. Sugden M. C., Watts D. L., Marshall C. E. Lipogenesis in response to an oral glucose load in fed and starved rats. Biosci Rep. 1981 Jun;1(6):469–476. doi: 10.1007/BF01121580. [DOI] [PubMed] [Google Scholar]
  33. Sugden P. H., Newsholme E. A. Activities of choline acetyltransferase, acetylcholinesterase, glutamate decarboxylase, 4-aminobutyrate aminotransferase and carnitine acetyltransferase in nervous tissue from some vertebrates and invertebrates. Comp Biochem Physiol C. 1977;56(2):89–94. doi: 10.1016/0306-4492(77)90019-3. [DOI] [PubMed] [Google Scholar]
  34. Szepsi B., Freedland R. A. Effect of thyroid hormones on metabolism IV. Comparative aspects of enzyme responses. Am J Physiol. 1969 May;216(5):1054–1056. doi: 10.1152/ajplegacy.1969.216.5.1054. [DOI] [PubMed] [Google Scholar]
  35. TATA J. R., ERNSTER L., LINDBERG O., ARRHENIUS E., PEDERSEN S., HEDMAN R. The action of thyroid hormones at the cell level. Biochem J. 1963 Mar;86:408–428. doi: 10.1042/bj0860408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Taunton O. D., Stifel F. B., Greene H. L., Herman R. H. Rapid reciprocal changes in rat hepatic glycolytic enzyme and fructose diphosphatase activities following insulin and glucagon injection. J Biol Chem. 1974 Nov 25;249(22):7228–7239. [PubMed] [Google Scholar]
  37. Triscari J., Sullivan A. C. Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. Lipids. 1977 Apr;12(4):357–363. doi: 10.1007/BF02533638. [DOI] [PubMed] [Google Scholar]
  38. Watson J. A., Fang M., Lowenstein J. M. Tricarballylate and hydroxycitrate: substrate and inhibitor of ATP: citrate oxaloacetate lyase. Arch Biochem Biophys. 1969 Dec;135(1):209–217. doi: 10.1016/0003-9861(69)90532-3. [DOI] [PubMed] [Google Scholar]
  39. Zammit V. A., Corstorphine C. G. Changes in the proportion of acetyl-CoA carboxylase in the active form in rat liver. Effect of starvation, lactation and weaning. Biochem J. 1982 Jun 15;204(3):757–764. doi: 10.1042/bj2040757. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES