Uncoupling proteins and the molecular mechanisms of thyroid thermogenesis

Endocrinology

Volumn 157, Issue 2, 2016, Pages 455-462

  Solmonson, A ^a   Mills, E M ^a,b  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^b University of Texas at Austin   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

THYROID HORMONE; THYROID PEROXIDASE; TYROSINE; UNCOUPLING PROTEIN; UNCOUPLING PROTEIN 1; ION CHANNEL; MITOCHONDRIAL PROTEIN;

ADRENERGIC SYSTEM; BODY TEMPERATURE; BROWN ADIPOSE TISSUE; CORE TEMPERATURE; HUMAN; METABOLISM; NONHUMAN; NONSHIVERING THERMOGENESIS; OXIDATIVE PHOSPHORYLATION UNCOUPLING; PRIORITY JOURNAL; PROTEIN DEGRADATION; REGULATORY MECHANISM; REVIEW; SKELETAL MUSCLE; THERMOGENESIS; THERMOREGULATION; THYROID GLAND; ANIMAL; GENETICS; PHYSIOLOGY;

ADIPOSE TISSUE, BROWN; ANIMALS; HUMANS; ION CHANNELS; MITOCHONDRIAL PROTEINS; MUSCLE, SKELETAL; THERMOGENESIS; THYROID GLAND; THYROID HORMONES; UNCOUPLING PROTEIN 1;

EID: 84956884193     PISSN: 00137227     EISSN: 19457170     Source Type: Journal    
DOI: 10.1210/en.2015-1803     Document Type: Review

References (89)

1. Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiol Rev. 2006;86(2):435-464.
2. Mullur R, Liu Y-Y, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355-382.
3. Harper ME, Brand MD. The quantitative contributions of mitochondrial proton leak and ATP turnover reactions to the changed respiration rates of hepatocytes from rats of different thyroid status. J Biol Chem. 1993;268(20):14850-14860.
4. Oppenheimer JH, Schwartz HL, Lane JT, Thompson MP. Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. J Clin Invest. 1991;87(1):125-132.
5. Solanes G, Pedraza N, Calvo V, Vidal-Puig A, Lowell BB, Villarroya F. Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region. Biochem J. 2005;386(Pt 3):505-513.
6. Cannon B. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277-359.
7. Astrup A, Lundsgaard C, Madsen J, Christensen NJ. Enhanced thermogenic responsiveness during chronic ephedrine treatment in man. Am J Clin Nutr. 1985;42(1):83-94.
8. Silva JE. The thermogenic effect of thyroid hormone and its clinical implications. Ann Intern Med. 2003;139(3):205-213.
9. Silva JE, Larsen PR. Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature. 1983;305(5936):712-713.
10. Dumont JE, Willems C, Van Sande J, Nève P. Regulation of the release of thyroid hormones: role of cyclic AMP. Ann NY Acad Sci. 1971;185:291-316.
11. Silva JE, Larsen PR. Hormonal regulation of iodothyronine 5′-deiodinase in rat brown adipose tissue. Am J Physiol. 1986;251(6 Pt 1):E639-E643.
12. Bianco AC, Silva JE. Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest. 1987;79(1):295-300.
13. Drigo RAE, Fonseca TL, Werneck-de-Castro JPS, Bianco AC. Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling. Biochim Biophys Acta. 2013;1830(7):3956-3964.
14. Weinberger C, Thompson CC, Ong ES, Lebo R, Gruol DJ, Evans RM. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986;324(6098):641-646.
15. Sap J, Muñoz A, Damm K, et al. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986;324(6098):635-640.
16. Benbrook D, Pfahl M. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987; 238(4828):788-791.
17. Cao X, Kambe F, Moeller LC, Refetoff S, Seo H. Thyroid hormone induces rapid activation of Akt/protein kinase B-mammalian target of rapamycin-p70 S6K cascade through phosphatidylinositol 3-kinase in human fibroblasts. Mol Endocrinol. 2005;19(1):102-112.
18. Bergh JJ, Lin H-Y, Lansing L, et al. Integrin αVβ3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis. Endocrinology. 2005;146(7):2864-2871.
19. Jezek P, Jezek J. Sequence anatomy of mitochondrial anion carriers. FEBS Lett. 2003;534(1-3):15-25.
20. Lin CS, Klingenberg M. Isolation of the uncoupling protein from brown adipose tissue mitochondria. FEBS Lett. 1980;113(2):299-303.
21. Klingenberg M, Lin CS. Isolation and hydrodynamic characterization of the uncoupling protein from brown adipose tissue. Methods Enzymol. 1986;126:490-498.
22. Klingenberg M, Winkler E. Reconstitution of an H+ translocator, the "uncoupling protein" from brown adipose tissue mitochondria, in phospholipid vesicles. Methods Enzymol. 1986;127:772-779.
23. Klingenberg M, Winkler E. The reconstituted isolated uncoupling protein is a membrane potential driven H+ translocator. EMBO J. 1985;4(12):3087-3092.
24. Blondin DP, Labbé SM, Phoenix S, et al. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol (Lond). 2015;593(3): 701-714.
25. Cunningham SA, Wiesinger H, Nicholls DG. Quantification of fatty acid activation of the uncoupling protein in brown adipocytes and mitochondria from the guinea pig. Eur J Biochem. 1986;157(2): 415-420.
26. Strieleman PJ, Schalinske KL, Shrago E. Fatty acid activation of the reconstituted brown adipose tissue mitochondria uncoupling protein. J Biol Chem. 1985;260(25):13402-13405.
27. Deykin D, Vaughan M. Release of free fatty acids by adipose tissue from rats treated with triiodothyronine or propylthiouracil. J Lipid Res. 1963;4(2):200-203.
28. Wang S, Subramaniam A, Cawthorne MA, Clapham JC. Increased fatty acid oxidation in transgenic mice overexpressing UCP3 in skeletal muscle. Diabetes Obes Metab. 2003;5(5):295-301.
29. Cannon B, Hedin A, Nedergaard J. Exclusive occurrence of thermogenin antigen in brown adipose tissue. FEBS Lett. 1982;150(1): 129-132.
30. Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB. UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun. 1997;235(1):79-82.
31. Boss O, Samec S, Paoloni-Giacobino A, et al. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett. 1997;408(1):39-42.
32. Fleury C, Neverova M, Collins S, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet. 1997; 15(3):269-272.
33. Lanni A, Moreno M, Lombardi A, Goglia F. Thyroid hormone and uncoupling proteins. FEBS Let. 2003;543(1-3):5-10.
34. Barbe P, Larrouy D, Boulanger C, et al. Triiodothyronine-mediated up-regulation of UCP2 and UCP3mRNAexpression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes. FASEB J. 2001;15(1):13-15.
35. Masaki T, Yoshimatsu H, Kakuma T, Hidaka S, Kurokawa M, Sakata T. Enhanced expression of uncoupling protein 2 gene in rat white adipose tissue and skeletal muscle following chronic treatment with thyroid hormone. FEBS Lett. 1997;418(3):323-326.
36. Gong DW, He Y, Karas M, Reitman M. Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, β3-adrenergic agonists, and leptin. J Biol Chem. 1997;272(39):24129-24132.
37. Lago CU, Nowinski SM, Rundhaug JE, et al. Mitochondrial respiratory uncoupling promotes keratinocyte differentiation and blocks skin carcinogenesis. Oncogene. 2012;31(44):4725-4731.
38. Matthias A, Ohlson KB, Fredriksson JM, Jacobsson A, Nedergaard J, Cannon B. Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty SCID-induced thermogenesis. J Biol Chem. 2000;275(33):25073-25081.
39. Bezaire V, Spriet LL, Campbell S, et al. Constitutive UCP3 overexpression at physiological levels increases mouse skeletal muscle capacity for fatty acid transport and oxidation. FASEB J. 2005;19(8): 977-979.
40. MacLellan JD, Gerrits MF, Gowing A, Smith PJS, Wheeler MB, Harper M-E. Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without uncoupling respiration in muscle cells. Diabetes. 2005;54(8):2343-2350.
41. Larkin S, Mull E, Miao W, et al. Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone. Biochem Biophys Res Commun. 1997;240(1):222-227.
42. Enerback S, Jacobsson A, Simpson EM, Guerra C. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997;387(6628):90-94.
43. Vidal-Puig AJ, Grujic D, Zhang CY, et al. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem. 2000; 275(21):16258-16266.
44. Flandin P, Lehr L, Asensio C, et al. Uncoupling protein-3 as a molecular determinant of the action of 3,5,3′-triiodothyronine on energy metabolism. Endocrine. 2009;36(2):246-254.
45. Vozza A, Parisi G, De Leonardis F, et al. UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci USA. 2014;111(3):960-965.
46. Mao W, Yu XX, Zhong A, et al. UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett. 1999;443(3):326-330.
47. Sanchis D, Fleury C, Chomiki N, et al. BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast. J Biol Chem. 1998;273(51):34611-34615.
48. Yu XX, Mao W, Zhong A, et al. Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation. FASEB J. 2000;14(11):1611-1618.
49. Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the CNS: in support of function and survival. Nat Rev Neurosci. 2005;6(11):829-840.
50. de Jesus LA, Carvalho SD, Ribeiro MO, et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest. 2001;108(9):1379-1385.
51. Carvalho SD, Kimura ET, Bianco AC, Silva JE. Central role of brown adipose tissue thyroxine 5′-deiodinase on thyroid hormonedependent thermogenic response to cold. Endocrinology. 1991; 128(4):2149-2159.
52. Christoffolete MA, Linardi CCG, de Jesus L, et al. Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis. Diabetes. 2004; 53(3):577-584.
53. Silva JE. The multiple contributions of thyroid hormone to heat production. J Clin Invest. 2001;108(1):35-37.
54. Bianco AC, Sheng XY, Silva JE. Triiodothyronine amplifies norepinephrine stimulation of uncoupling protein gene transcription by a mechanism not requiring protein synthesis. J Biol Chem. 1988; 263(34):18168-18175.
55. Branco M, Ribeiro M, Negrão N, Bianco AC. 3,5,3′-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity. Am J Physiol. 1999;276(1 Pt 1):E179-E187.
56. Rubio A, Raasmaja A, Maia AL, Kim KR, Silva JE. Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. β1-and β2-adrenergic receptors and cyclic adenosine 3′,5′-monophosphate generation. Endocrinology. 1995;136(8):3267-3276.
57. Jimenez M, Léger B, Canola K, et al. β1/β2/β3-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting. FEBS Lett. 2002;530(1-3):37-40.
58. Matsukawa T, Mano T, Gotoh E, Minamisawa K, Ishii M. Altered muscle sympathetic nerve activity in hyperthyroidism and hypothyroidism. J Auton Nerv Syst. 1993;42(2):171-175.
59. Rabelo R, Reyes C, Schifman A, Silva JE. Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone. Endocrinology. 1996;137(8):3478-3487.
60. Golozoubova V, Gullberg H, Matthias A, Cannon B, Vennström 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(2):384-401.
61. Wikström L, Johansson C, Saltó C, et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. EMBO J. 1998;17(2):455-461.
62. Johansson C, Göthe S, Forrest D. Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-β or both α1 and β. Am J Physiol. 1999;276(6 Pt 2):H2006-H2012.
63. Puigserver P, Wu Z, Park CW, Graves R, Wright M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92(6):829-839.
64. Marrif H, Schifman A, Stepanyan Z, Gillis M-A, et al. Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-α gene products. Endocrinology. 2005;146(7):2872-2884.
65. Ribeiro MO, Carvalho SD, Schultz JJ, Chiellini G, Scanlan TS, Bianco AC, Brent GA. Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform specific. J Clin Invest. 2001;108(1):97-105.
66. Klaus S, Ely M, Encke D, Heldmaier G. Functional assessment of white and brown adipocyte development and energy metabolism in cell culture. Dissociation of terminal differentiation and thermogenesis in brown adipocytes. J Cell Sci. 1995;108(10):3171-3180.
67. Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPARγ agonists Induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab 2012;15(3):395-404.
68. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptorγ (PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285(10):7153-7164.
69. Wu J, Boström P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012;150(2): 366-376.
70. Lee J-Y, Takahashi N, Yasubuchi M, et al. Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. Am J Physiol Cell Physiol. 2012;302(2):C463-C472.
71. Jiang W, Miyamoto T, Kakizawa T, et al. Expression of thyroid hormone receptor alpha in 3T3-L1 adipocytes; triiodothyronine increases the expression of lipogenic enzyme and triglyceride accumulation. J Endocrinol. 2004;182(2):295-302.
72. Mills EM, Banks ML, Sprague JE, Finkel T. Pharmacology: uncoupling the agony from ecstasy. Nature 2003;426(6965):403-404.
73. Zhang Q, Miao Q, Ye H, et al. The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study. Weng J, Pozzilli P, eds. Diabetes Metab Res Rev. 2014;30(6):513-520.
74. Astrup A, Simonsen L, Bülow J, Madsen J, Christensen NJ. Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle. Am J Physiol. 1989;257(3 Pt 1):E340-E345.
75. Cypess AM, Chen Y-C, Sze C, et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci USA. 2012;109(25):10001-10005.
76. Sprague JE, Mallett NM, Rusyniak DE, Mills E. UCP3 and thyroid hormone involvement in methamphetamine-induced hyperthermia. Biochem Pharmacol. 2004;68(7):1339-1343.
77. Leijendekker WJ, van Hardeveld C, Elzinga G. Heat production during contraction in skeletal muscle of hypothyroid mice. Am J Physiol. 1987;253(2 Pt 1):E214-E220.
78. Brand MD, Steverding D, Kadenbach B, Stevenson PM, Hafner RP. The mechanism of the increase in mitochondrial proton permeability induced by thyroid hormones. Eur J Biochem. 1992;206(3):775-781.
79. Sprague JE, Yang X, Sommers J, Gilman TL, Mills EM. Roles of norepinephrine, free fatty acids, thyroid status, and skeletal muscle uncoupling protein 3 expression in sympathomimetic-induced thermogenesis. J Pharmacol Exp Ther. 2006;320(1):274-280.
80. Simonides WS, van Hardeveld C. Thyroid hormone as a determinant of metabolic and contractile phenotype of skeletal muscle. Thyroid. 2008;18(2):205-216.
81. Dawson AG. Oxidation of cytosolic NADH formed during aerobic metabolism in mammalian cells. Trends Biochem Sci. 1979;4(8): 171-176.
82. Klingenberg M. Localization of the glycerol-phosphate dehydrogenase in the outer phase of the mitochondrial inner membrane. Eur J Biochem. 1970;13(2):247-252.
83. Alfadda A, DosSantos RA, Stepanyan Z, Marrif H, Silva JE. Mice with deletion of the mitochondrial glycerol-3-phosphate dehydrogenase gene exhibit a thrifty phenotype: effect of gender. Am J Physiol Regul Integr Comp Physiol. 2004;287(1):R147-R156.
84. DosSantos RA, Alfadda A, Eto K, Kadowaki T, Silva JE. Evidence for a compensated thermogenic defect in transgenic mice lacking the mitochondrial glycerol-3-phosphate dehydrogenase gene. Endocrinology. 2003;144(12):5469-5479.
85. Warner A, Rahman A, Solsjö P, et al. Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor α1. Proc Natl Acad Sci USA. 2013;110(40):16241-16246.
86. Pelletier P, Gauthier K, Sideleva O, Samarut J, Silva JE. Mice lacking the thyroid hormone receptor-α gene spend more energy in thermogenesis, burn more fat, and are less sensitive to high-fat diet-induced obesity. Endocrinology. 2008;149:6471-6486.
87. Schneider MJ, Fiering SN, Pallud SE, Parlow AF, St Germain DL, Galton VA. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol. 2001;15:2137-2148.
88. Hall JA, Ribich S, Christoffolete MA, Simovic G, Correa-Medina M, Patti ME, Bianco AC. Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology. 2010;151:4573-4582.
89. Castillo M, Hall JA, Correa-Medina M, Ueta C, Kang HW, Cohen DE, Bianco AC. Disruption of thyroid hormone activation in type 2 deiodinase knockout mice causes obesity with glucose intolerance and liver steatosis only at thermoneutrality. Diabetes. 2011;60: 1082-1089.