Download PDF
Horm Metab Res 2005; 37(9): 545-549
DOI: 10.1055/s-2005-870420
Review
© Georg Thieme Verlag KG Stuttgart · New York

Cold Adaptation and Thyroid Hormone Metabolism

P.  Laurberg1 , S.  Andersen1 , J.  Karmisholt1
  • 1Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
Further Information

Publication History

Received 15 December 2004

Accepted after Revision 26 March 2005

Publication Date:
20 September 2005 (online)

Also available at
    Permissions and Reprints

Abstract

Resting oxygen consumption and energy expenditure is sensitive to slight alterations in thyroid function. This means that timing and magnitude of cold adaptation would to some extent depend on thyroid function. Local thyroid hormone metabolism is important for energy expenditure and dissipation of heat in special tissues. Recruitment of brown adipocytes and upregulation of uncoupling protein 1 in mitochondria depends on high tissue T3 concentrations. Most of this T3 is derived from local 5' deiodination of T4. Brown fat is vital for cold exposed mice and rats, and may be important for temperature adaptation in human neonates. The role of thyroid hormone metabolism in adult human cold adaptation has not been finally clarified. Hypothetically, cold exposure may enhance T3 production by deiodination of T4 in skeletal muscle, which may enhance heat production in muscle via a change in muscle fiber type. Another hypothetical possibility is recruitment of brown adipocytes embedded in white adipose tissue in human adults. Understanding cold adaptation in human adults may lead to development of new drugs against obesity.

Key words

Arctic residence - Brown adipose tissue - Cold adaptation - Obesity - Thyroid hormone metabolism - Uncoupling protein

References

  • 1 Nicholls D G, Locke R M. Thermogenic mechanisms in brown fat.  Physiol Rev. 1984;  64 1-64
    CrossrefPubMedSearch in Google Scholar
  • 2 Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance.  Physiol Rev. 2004;  84 277-359
    CrossrefPubMedSearch in Google Scholar
  • 3 Smith R E, Hoijer D J. Metabolism and cellular function in cold acclimation.  Physiol Rev. 1962;  42 60-142
    PubMedSearch in Google Scholar
  • 4 Al-Adsani H, Hoffer L J, Silva J E. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement.  J Clin Endocrinol Metab. 1997;  82 1118-1125
    CrossrefPubMedSearch in Google Scholar
  • 5 Silva J E. The thermogenic effect of thyroid hormone and its clinical implications.  Ann Intern Med. 2003;  139 205-213
    PubMedSearch in Google Scholar
  • 6 Nedergaard J, Lindberg O. Norepinephrine-stimulated fatty-acid release and oxygen consumption in isolated hamster brown-fat cells. Influence of buffers, albumin, insulin and mitochondrial inhibitors.  Eur J Biochem. 1979;  95 139-145
    CrossrefPubMedSearch in Google Scholar
  • 7 Garlid K D, Jaburek M, Jezek P. The mechanism of proton transport mediated by mitochondrial uncoupling proteins.  FEBS Lett. 1998;  438 10-14
    CrossrefPubMedSearch in Google Scholar
  • 8 Sellers E A, You S S. Role of the thyroid in metabolic responses to a cold environment.  Am J Physiol. 1950;  163 81-91
    PubMedSearch in Google Scholar
  • 9 Silva J E, Larsen P R. Adrenergic activation of triiodothyronine production in brown adipose tissue.  Nature. 1983;  305 712-713
    CrossrefPubMedSearch in Google Scholar
  • 10 Silva J E, Larsen P R. Potential of brown adipose tissue type II thyroxine 5'-deiodinase as a local and systemic source of triiodothyronine in rats.  J Clin Invest. 1985;  76 2296-2305
    PubMedSearch in Google Scholar
  • 11 Bianco A C, Salvatore D, Gereben B, Berry M J, Larsen P R. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.  Endocr Rev. 2002;  23 38-89
    CrossrefPubMedSearch in Google Scholar
  • 12 De Jesus L A, Carvalho S D, Ribeiro M O, Schneider M, Kim S W, Harney J W, Larsen P R, Bianco A C. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue.  J Clin Invest. 2001;  108 1379-1385
    CrossrefPubMedSearch in Google Scholar
  • 13 Ribeiro M O, Carvalho S D, Schultz J J, Chiellini G, Scanlan T S, Bianco A C, Brent G A. Thyroid hormone sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform specific.  J Clin Invest. 2001;  108 97-105
    CrossrefPubMedSearch in Google Scholar
  • 14 Golozoubova V, Gullberg H, Matthias A, Cannon B, Vennstrom B, Nedergaard J. Depressed thermogenesis but competent brown adipose tissue recruitment in mice devoid of all hormone-binding thyroid hormone receptors.  Mol Endocrinol. 2004;  18 384-401
    PubMedSearch in Google Scholar
  • 15 Pazos-Moura C C, Moura E G, Dorris M L, Rehnmark S, Melendez L, Silva J E, Taurog A. Effect of iodine deficiency and cold exposure on thyroxine 5’-deiodinase activity in various rat tissues.  Am J Physiol. 1991;  260 175-182
    PubMedSearch in Google Scholar
  • 16 Zaninovich A A, Rebagliati I, Raices M, Ricci C, Hagmuller K. Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats.  J Appl Physiol. 2003;  95 1584-1590
    PubMedSearch in Google Scholar
  • 17 Golozoubova V, Hohtola E, Matthias A, Jacobsson A, Cannon B, Nedergaard J. Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold.  FASEB J. 2001;  15 2048-2050
    PubMedSearch in Google Scholar
  • 18 Jung R T, Leslie P, Nicholls D G, Cunningham S, Isles T E. Energy expenditure in normal and diabetic man: the role of brown adipose tissue.  Health Bull (Edinb). 1988;  46 55-62
    PubMedSearch in Google Scholar
  • 19 Depocas F. Chemical thermogenesis in the functionally eviscerated cold-acclimated rat.  Can J Med Sci. 1958;  36 691-699
    PubMedSearch in Google Scholar
  • 20 Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino J P. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression.  FEBS Lett. 1997;  408 39-42
    CrossrefPubMedSearch in Google Scholar
  • 21 Larkin S, Mull E, Miao W, Pittner R, Albrandt K, Moore C, Young A, Denaro M, Beaumont K. Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone.  Biochem Biophys Res Commun. 1997;  240 222-227
    CrossrefPubMedSearch in Google Scholar
  • 22 Lean M EJ. Brown adipose tissue in humans.  Proc Nutr Soc. 1989;  48 243-256
    CrossrefPubMedSearch in Google Scholar
  • 23 Burrow G N, Fisher D A, Larsen P R. Maternal and fetal thyroid function.  N Engl J Med. 1994;  331 1072-1078
    CrossrefPubMedSearch in Google Scholar
  • 24 Oden J, Freemark M. Thyroxine supplementation in preterm infants: critical analysis.  Curr Opin Pediatr. 2002;  14 447-452
    CrossrefPubMedSearch in Google Scholar
  • 25 Garruti G, Ricquier D. Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans.  Int J Obes Relat Metab Disord. 1992;  16 383-390
    PubMedSearch in Google Scholar
  • 26 Ricquier D, Nechad M, Mory G. Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma.  J Clin Endocrinol Metab. 1982;  54 803-807
    PubMedSearch in Google Scholar
  • 27 Paakkonen T, Leppaluoto J. Cold exposure and hormonal secretion: a review.  Int J Circumpolar Health. 2002;  61 265-276
    PubMedSearch in Google Scholar
  • 28 Nagata H, Izumiyama T, Kamata K, Kono S, Yukimura Y. An increase of plasma triiodothyronine concentration in man in a cold environment.  J Clin Endocrinol Metab. 1976;  43 1153-1156
    PubMedSearch in Google Scholar
  • 29 Reed H L, Brice D, Shakir K M, Burman K D, D’Alesandro M M, O’Brian J T. Decreased free fraction of thyroid hormones after prolonged Antarctic residence.  J Appl Physiol. 1990;  69 1467-1472
    PubMedSearch in Google Scholar
  • 30 Leppaluoto J, Sikkila K, Hassi J. Seasonal variation of serum TSH and thyroid hormones in males living in subarctic environmental conditions.  Int J Circumpolar Health. 1998;  57 383-385
    PubMedSearch in Google Scholar
  • 31 Sawhney R C, Malhotra A S, Nair C S, Bajaj A C, Rajan K C, Pal K, Prasad R, Basu M. Thyroid function during a prolonged stay in Antarctica.  Eur J Appl Physiol Occup Physiol. 1995;  72 127-133
    PubMedSearch in Google Scholar
  • 32 Do N V, Mino L, Merriam G R, LeMar H, Case H S, Palinkas L A, Reedy K, Reed H L. Elevation in serum thyroglobulin during prolonged Antarctic residence: effect of thyroxine supplement in the polar 3,5,3’-triiodothyronine syndrome.  J Clin Endocrinol Metab. 2004;  89 1529-1533
    CrossrefPubMedSearch in Google Scholar
  • 33 Reed H L, Silverman E D, Shakir K M, Dons R, Burman K D, O’Brian J T. Changes in serum triiodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome.  J Clin Endocrinol Metab. 1990;  70 965-974
    PubMedSearch in Google Scholar
  • 34 Laurberg P. Thyroxine and 3,5,3'-triiodothyronine content of thyroglobulin in thyroid needle aspirates in hyperthyroidism and hypothyroidism.  J Clin Endocrinol Metab. 1987;  64 969-974
    PubMedSearch in Google Scholar
  • 35 Laurberg P, Jakobsen P E, Hoeck H C, Vestergaard P. Growth hormone and thyroid function: is secondary thyroid failure underdiagnosed in growth hormone deficient patients?.  Thyroidology. 1994;  6 73-79
    PubMedSearch in Google Scholar
  • 36 Reed H L, Quesada M, Hesslink R L Jr, D’Alesandro M M, Hays M T, Christopherson R J, Turner B V, Young B A. Changes in serum triiodothyronine kinetics and hepatic type I 5'-deiodinase activity of cold-exposed swine.  Am J Physiol. 1994;  266 786-795
    PubMedSearch in Google Scholar
  • 37 Wassen F W, Klootwijk W, Kaptein E, Duncker D J, Visser T J, Kuiper G G. Characteristics and thyroid state-dependent regulation of iodothyronine deiodinases in pigs.  Endocrinology. 2004;  145 4251-4263
    CrossrefPubMedSearch in Google Scholar
  • 38 De Meis L. Role of the sarcoplasmic reticulum Ca2+-ATPase on heat production and thermogenesis.  Biosci Rep. 2001;  21 113-137
    CrossrefPubMedSearch in Google Scholar
  • 39 Everts M E. Effects of thyroid hormones on contractility and cation transport in skeletal muscle.  Acta Physiol Scand. 1996;  156 325-333
    CrossrefPubMedSearch in Google Scholar
  • 40 Clausen T, Van Hardeveld C, Everts M E. Significance of cation transport in control of energy metabolism and thermogenesis.  Physiol Rev. 1991;  71 733-774
    PubMedSearch in Google Scholar
  • 41 Simonides W S, Thelen M H, van der Linden C G, Muller A, van Hardeveld C. Mechanism of thyroid-hormone regulated expression of the SERCA genes in skeletal muscle: implications for thermogenesis.  Biosci Rep. 2001;  21 139-154
    CrossrefPubMedSearch in Google Scholar
  • 42 Reis M, Farage M, de Meis L. Thermogenesis and energy expenditure: control of heat production by the Ca(2+)-ATPase of fast and slow muscle.  Mol Membr Biol. 2002;  19 301-310
    PubMedSearch in Google Scholar
  • 43 Hosoi Y, Murakami M, Mizuma H, Ogiwara T, Imamura M, Mori M. Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells.  J Clin Endocrinol Metab. 1999;  84 3293-3300
    CrossrefPubMedSearch in Google Scholar
  • 44 Himms-Hagen J. Exercise in a pill: feasibility of energy expenditure targets.  Curr Drug Targets CNS Neurol Disord. 2004;  3 389-409
    PubMedSearch in Google Scholar
  • 45 Magnus-Levy A. Ueber den respiratorischen Gaswechsel unter dem Einfluss der Thyreoidea sowie unter verschiedenen pathologischen Zustaenden.  Berliner Klinische Wochenschrift. 1895;  30 650-652
    PubMedSearch in Google Scholar

Peter Laurberg

Department of Endocrinology and Medicine

Aalborg Hospital · 9000 Aalborg · Denmark

Phone: +45 99 32 17 39

Fax: +45 98 12 02 53

Email: laurberg@aas.nja.dk