Summary
Despite their enhanced endogenous de novo cholesterol synthesis, hyperthyroid patients exhibit decreased total and low-density lipoprotein (LDL) cholesterol levels in the serum because of a concomitant increase in LDL catabolism, cholesterol excretion by bile and a reduced enterohepatic bile acid circulation. Hypothyroidism exhibits a reduction (1) in the synthesis of cholesterol and (2) in LDL catabolism, whereas cholesterol reabsorption is unchanged or even enhanced. In addition, obese hypothyroid patients showed an increased cholesterol synthesis which is independent of thyroid hormones and which contributes to the observed LDL cholesterolaemia. Thyroid hormones per se have only a minor influence on plasma triglyceride (TG) levels, but they induce an acceleration of TG turnover and chylomicron clearance rate. In addition, the hepatic lipogenic capacity is increased in hyperthyroidism and reduced in hypothyroidism. However, hepatic total and very low-density lipoprotein (VLDL) triglyceride output is decreased by thyroid hormones due to a reduced re-esterification and a simultaneously increased oxidation of newly synthesized fatty acids. Hypothyroid livers, by contrast, reveal an increased VLDL secretion. Despite their reduced lipogenesis, obese hypothyroidism is often accompanied by a hypertriglyceridaemia type III. The simultaneous stimulation of the synthesis of fatty acids, which are still in part converted to TG, and the degradation of TG contributes to the enhanced thermogenesis in hyperthyroid patients. The concentration and turnover of free fatty acids (FFA) are increased in hyperthyroidism, resulting from a thyroid hormone-induced increase in: (1) lipolysis, explained by an increased adipose tissue sensitivity for lipolytic hormones; and (2) oxidation of fatty acids to CO2 as well as to ketone bodies (KB). Accordingly, hyperthyroid patients often show ketonaemia. Hypothyroidism does not significantly affect the serum concentrations of FFA and KB.
Similar content being viewed by others
References
Abrams JJ, Grundy SM, Ginsberg H (1981) Metabolism of plasma triglycerides in hypothyroidism and hyperthyroidism in man. J Lipid Res 22:307–322
Abrams JJ, Grundy SM (1981) Cholesterol metabolism in hypothyroidism and hyperthyroidism in man. J Lipid Res 22:323–338
Baquer NZ, Cascales M, McLean P et al (1976) 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 68:403–413
Bray GA (1969) Effect of diet and triiodothyronine on the activity of glycerolphosphatedehydrogenase and on the metabolism of glucose and pyruvate by adipose tissue of obese patients. J Clin Invest 48:1413–1422
Ciaraldi TP, Marinetti GV (1978) Hormone action at the membrane level. VIII Adrenergic receptors in rat heart and adipocytes and their modulation by thyroxine. Biochim Biophys Acta 541:334–346
Chait A, Bierman EL, Albers JL (1979) Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts. J Clin Endocrin Metab 48:887–889
Chopra IJ (1981) Triiodothyronines in health and disease. Springer, Berlin Heidelberg New York
Das DK (1980) Regulation of hepatic fatty acid synthesizing enzymes of diabetic animals by thyroid hormone. Arch Biochem Biophys 203:25–36
Diamant S, Gorin E, Shafrir E (1972) Enzyme activities related to fatty-acid synthesis in liver and adipose tissue of rats treated with triiodothyronine. Eur J Biochem 26:553–559
Eaton RP, Steinberg D, Thompson RH (1965) Relationship between free fatty acid turnover and total body oxygen consumption in the euthyroid and hyperthyroid states. J Clin Invest 44:247–260
Engelken SF, Eaton RP (1980) Thyroid hormone-induced dissociation between plasma triglyceride and cholesterol regulation in the rat. Endocrinology 107:208–214
Faas FH, Carter WJ, Wynn JO (1977) An indirect thyroxine stimulation of microsomal fatty acid desaturation in vitro. Arch Biochem Biophys 182:71–81
Fain JN (1980) Hormonal regulation of lipid mobilization from adipose tissue. In: Litwack G (ed) Biochemical actions of hormones, Vol VII. Academic Press, New York, pp 119–204
Fain JN (1981) Catecholamine-thyroid hormone interactions in liver and adipose tissue. Life Sci 28:1745–1754
Feingold KR, Wiley MH, MacRae G et al (1980) Influence of thyroid hormone status on mevalonate metabolism in rats. J Clin Invest 66:646–654
Floren CH, Nilsson A (1981) Effects of hypothyroidism and cholesterol feeding on the clearance of chylomicron remnants in vivo and by rat hepatocyte monolayers. Eur J Clin Invest 11:11–18
Fray H (1967) Uptake of free fatty acids by normal and thyrotoxic skeletal muscle. Acta Endocrin 56:203–208
Glenny HP, Brindley DN (1978) The effect of cortisol, corticotropin, and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver. Biochem J 176:777–784
Gnoni GV, Landriscina C, Quagliariello E (1978) Mechanism of triiodothyronine stimulation on microsomal fatty acid chain elongation synthesis in rat liver. FEBS Lett 94:179–182
Gnoni GV, Landriscina C, Quagliariello E (1980) Thyroid hormone stimulation of lipogenesis in isolated rat hepatocytes. Biochem Med 24:336–347
Gold MJ, Scott C, Spitzer JJ (1967) Myocardial metabolism of free fatty acids in control, hyperthyroid and hypothyroid dogs. Am J Physiol 213:239–245
Goswami A, Rosenberg IN (1978) Thyroid hormone modulation of epinephrine induced lipolysis in rat adipocytes: A possible role of calcium. Endocrinology 103:2223–2233
De Groot LJ (1979) Thyroid Hormone Action. In: De Groot LJ, Cahill GF, Odell WD et al. (eds) Endocrinology. Grune & Stratton, New York, pp 357–363
Guidicelli Y (1978) Thyroid-hormone modulation of the number ofβ-adrenergic receptors in rat fat-cell membranes. Biochem J 176:1007–1010
Hagenfeldt L, Wennlund A, Felig P et al (1981) Turnover and splanchnic metabolism of free fatty acids in hyperthyroid patients. J Clin Invest 67:1672–1677
Hazzard WR, Bierman EL (1972) Aggravation of broadβ-disease in hypothyroidism. Arch Int Med 130:822–825
Hoch FL, Subramanian C, Dhopeshwarkar GA et al (1981) Thyroid control over biomembranes VI. Lipids in liver mitochondria and microsomes of hypothyroid rats. Lipids 16:328–335
Hulbert AJ (1978) The thyroid hormones: A thesis concerning their action. J Theor Biol 73:81–100
Ingbar SH, Woeber KA (1981) The Thyroid Gland. In: Williams RH (ed) Textbook of Endocrinology, 6th Edition. WB Saunders, Philadelphia, pp 117–247
Van Inwegen RG, Robison GA, Thompson WJ et al (1975) Cyclic nucleotide phosphodiesterase and thyroid hormones. J Biol Chem 250:2452–2456
Kaciuba-Uscilko H, Dudley GA, Terjung RL (1980) Influence of thyroid status on skeletal muscle LPL-activity and TG-uptake. Am J Physiol 238:E 518–523
Keyes WG, Wilcox HG, Heimberg M (1981) Formation of the very low density lipoprotein and metabolism of [1-14C-]oleate by perfused livers from rats treated with triiodothyronine or propylthiouracil. Metabolism 30:135–146
Krishna G, Hynie S, Brodie BB (1968) Effects of thyroid hormones on adenylcyclase in adipose tissue and on free fatty acid mobilization. Proc Natl Acad Sci USA 59:884–889
Kutty KM, Bryant DG, Farid NR (1978) Serum lipids in hypothyroidism. J Clin Endocrinol Metab 46:55–60
Laker ME, Mayes PA (1981) Effect of hyperthyroidism and hypothyroidism on lipid and carbohydrate metabolism of the perfused rat liver. Biochem J 196:247–255
Lehtonen MA, Savolainen MJ, Hassinen IE (1979) Hormonal regulation of hepatic soluble phosphatidate phosphohydrolase. FEBS Lett 99:162–166
Lithell H, Boberg J, Hellsing K et al (1981) Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. Eur J Clin Invest 11:3–10
Loeb JN (1979) Metabolic Changes. In: Ingbar SH, Werner SC (eds) The Thyroid. Harper & Row, New York, pp 705–712 and pp 872–877
Mariash CN, Kaiser FE, Schwartz HL et al (1980) Synergism of thyroid hormone and high carbohydrate diet in the induction of lipogenic enzymes in the rat. J Clin Invest 65:1126–1134
Mathe D, Chevallier F (1976) Effects of the thyroid state on cholesterol metabolism in the rat. Biochim Biophys Acta 441:155–164
Mishkel MP, Crowther SM (1977) Hypothyroidism, an important cause of reversible hyperlipidemia. Clin Chim Acta 74:139–151
Müller MJ, Köster H, Seitz HJ (1981) Effect of thyroid state on ketogenic capacity of the isolated-perfused liver of starved rats. Biochim Biophys Acta 666:475–481
Ness GC, Dugan RE, Lakshmanan MR et al (1973) Stimulation of hepaticβ-hydroxy-methyl-glutaryl Coenzyme A reductase activity in hypophysectomized rats by L-triiodothyronine. Proc Natl Acad Sci USA 70:3839–3842
Nikkilä EA, Kekki M (1972) Plasma triglyceride metabolism in thyroid disease. J Clin Invest 51:2103–2114
Nunez J, Correze C (1981) Interdependent effects of thyroid hormones and cAMP on lipolysis and lipogenesis in the fat cell. In: Dumont JE, Greengard P (eds) Adv Cyclic Nucleotide Res, Vol 14. Raven Press, New York, pp 539–555
Östman J, Arner P, Bolinder J et al (1981) Regulation of lipolysis in hyperthyroidism. Int J Obesity 5:665–670
Pasquini JM, Faryna de Raveglia I, Capitman N et al (1980) Differential effect of L-thyroxine on phospholipid biosynthesis in mitochondria and microsomal fraction. Biochem J 186:127–133
Redgrave TG, Snibson DA (1977) Clearance of chylomicron triacylglycerol and cholesteryl ester from the plasma of streptozotozin-induced diabetic and hypercholesterolemic hypothyroid rats. Metabolism 26:493–503
Roncari DAK, Murthy VK (1975) Effects of thyroid hormones on enzymes involved in fatty acid and glycerolipid synthesis. J Biol Chem 250:4134–4138
Sandhofer F, Sailer S, Braunsteiner H (1966) Fettsäure-und Triglyceridumsatz bei Schilddrüsenüberfunktion. Klin Wochenschr 44:1389–1393
Sandhofer F, Sailer S, Bolzano K et al (1967) Über die Wirkung einesβ-Rezeptorenblockers (Propranolol) auf die Umsatzrate der freien Fettsäuren und deren Einbaurate in Plasmatriglyceride bei Hyperthyreose. Schweiz Med Wochenschr 97:1319–1323
Saunders J, Hall SEH, Sönksen PH (1980) Glucose and free fatty acid turnover in thyrotoxicosis and hypothyroidism, before and after treatment. Clin Endocrinol (Oxf) 13:33–44
Schroeder F, Wilcox HG, Keyes WG et al (1982) Effects of thyroid status on the structure of the very low density lipoprotein secreted by the perfused liver. Endocrinology 110:551–562
Scottolini AG, Bhagavan NV, Oshiro TH et al (1980) Serum high-density lipoprotein cholesterol concentrations in hypo- and hyperthyroidism. Clin Chem 26:584–587
Sestoft L (1980) Metabolic aspects of the calorigenic effect of thyroid hormone in mammals. Clin Endocrinol 13:489–506
Sestoft L, Bartels PD (1980) Thyroid hormone-induced changes in the regulatory interrelationship between gluconeogenesis and ketogenesis in perfused rat liver. Biochim Biophys Acta 633:56–67
Sudgen MC, Watts DI, Marshall CE (1981) Regulation of hepatic lipogenesis in starved and diabetic animals by thyroid hormone. Bioscience Rep 1:757–764
Sykes M, Cnoop-Koopmans WM, Julien P et al (1981) The effects of hypothyroidism, age, and nutrition on LDL-catabolism in the rat. Metabolism 30:733–738
Tulloch BR, Lewis B, Russell Fraser T (1973) Triglyceride metabolism in thyroid disease. Lancet I:391–394
Wahlquist ML, Fidge NH, Lomas F (1977) Lipoprotein composition in hypothyroidism. Clin Chim Acta 77:269–274
Wilson DE, Jubiz W, Flowers CM et al (1977) Tissue lipoprotein lipase in the hyperthyroid rat: effect of growth and aging. Atherosclerosis 26:353–362
Wirth A, Holm G, Lindstedt G et al (1981) Thyroid hormones and lipolysis in physically trained rats. Metabolism 30:237–241
Young DL, Lynen F (1969) Enzymatic regulation of 3-snphosphatidylcholine and triacylglycerol synthesis in states of altered lipid metabolism. J Biol Chem 244:377–383
Author information
Authors and Affiliations
Additional information
Thyroid hormones are defined as 3,5,3′,5′-tetraiodothyronine (thyroxine-T4) and its deiodinated or non-deiodinated metabolic products providing thyromimetic activity, mainly 3,5,3′-triiodothyronine (T3)
Rights and permissions
About this article
Cite this article
Müller, M.J., Seitz, H.J. Thyroid hormone action on intermediary metabolism. Klin Wochenschr 62, 49–55 (1984). https://doi.org/10.1007/BF01769663
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01769663