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Type I iodothyronine 5′-deiodinase mRNA and activity is increased in adipose tissue of obese subjects

Abstract

Differentiation and metabolism of adipose tissue are modulated by thyroid hormones (THs), but relatively little is known about the metabolism of THs in this tissue. Expression of the genes for type I iodothyronine 5′-deiodinase (D1), leptin (LEP) and stearoyl-CoA desaturase 1 (SCD-1) was evaluated in omental (OM) and subcutaneous (SC) fat using a cohort of 70 humans. Activities of iodothyronine deiodinases (D1, D2 and D3) were assessed in a randomly selected subpopulation of 19 subjects. D1 expression was upregulated in both OM (P=0.011) and SC (P=0.003) fat of obese subjects. Concomitantly, OM (P=0.002) and SC (P=0.028) LEP expression were increased in obesity, associated with both D1 mRNA (r=0.315, P=0.014) and activity (r=0.647, P=0.023) and inversely related to SCD-1 (r=−0.266, P=0.034) expression in SC fat. Also D1 (but not D2 and D3) activity was increased in OM (fourfold, P=0.010) and SC (eightfold, P=0.004) fat of obese when compared with non-obese subjects and correlated in both OM (r=0.528, P=0.036) and SC (r=0.749, P=0.005) fat with body mass index. Our results document increased D1 gene expression and activity in adipose tissue of obese humans and suggest a role of 3,5,3′-triiodo-L-thyronine formed by D1 in response to leptin in the modulation of adipose tissue metabolism.

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References

  1. Obregon MJ . Thyroid hormone and adipocyte differentiation. Thyroid 2008; 18: 185–195.

    Article  CAS  Google Scholar 

  2. Ailhaud G, Grimaldi P, Negrel R . Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr 1992; 12: 207–233.

    Article  CAS  Google Scholar 

  3. 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: 125–132.

    Article  CAS  Google Scholar 

  4. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR . Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 2002; 23: 38–89.

    Article  CAS  Google Scholar 

  5. Leonard JL, Mellen SA, Larsen PR . Thyroxine 5′-deiodinase activity in brown adipose tissue. Endocrinology 1983; 112: 1153–1155.

    Article  CAS  Google Scholar 

  6. Pavelka S, Kopecky P, Bendlova B, Stolba P, Vitkova I, Vobruba V et al. Tissue metabolism and plasma levels of thyroid hormones in critically ill very premature infants. Pediatr Res 1997; 42: 812–818.

    Article  CAS  Google Scholar 

  7. Macek Jilkova Z, Pavelka S, Flachs P, Hensler M, Kus V, Kopecky J . Modulation of type I iodothyronine 5′-deiodinase activity in white adipose tissue by nutrition: possible involvement of leptin. Physiol Res 2010; 59: 561–569.

    CAS  PubMed  Google Scholar 

  8. Araujo RL, Andrade BM, da Silva ML, Ferreira AC, Carvalho DP . Tissue-specific deiodinase regulation during food restriction and low replacement dose of leptin in rats. Am J Physiol Endocrinol Metab 2009; 296: E1157–E1163.

    Article  CAS  Google Scholar 

  9. Cabanelas A, Lisboa PC, Moura EG, Pazos-Moura CC . Leptin acute modulation of the 5′-deiodinase activities in hypothalamus, pituitary and brown adipose tissue of fed rats. Horm Metab Res 2006; 38: 481–485.

    Article  CAS  Google Scholar 

  10. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432.

    Article  CAS  Google Scholar 

  11. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002; 415: 339–343.

    Article  CAS  Google Scholar 

  12. Cohen P, Friedman JM . Leptin and the control of metabolism: role for stearoyl-CoA desaturase-1 (SCD-1). J Nutr 2004; 134: 2455S–2463S.

    Article  CAS  Google Scholar 

  13. Paton CM, Ntambi JM . Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 2009; 297: E28–E37.

    Article  CAS  Google Scholar 

  14. Zhang W, Della-Fera MA, Hartzell DL, Hausman D, Baile CA . Adipose tissue gene expression profiles in ob/ob mice treated with leptin. Life Sci 2008; 83: 35–42.

    Article  CAS  Google Scholar 

  15. Fernandez-Real JM, Catalan V, Moreno-Navarrete JM, Gomez-Ambrosi J, Ortega FJ, Rodriguez-Hermosa JI et al. Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes. Nutr Metab (Lond) 2010; 7: 20.

    Article  Google Scholar 

  16. Ortega FJ, Mayas D, Moreno-Navarrete JM, Catalan V, Gomez-Ambrosi J, Esteve E et al. The gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue of obese subjects. Obesity (Silver Spring) 2009; 18: 13–20.

    Article  Google Scholar 

  17. Hube F, Lietz U, Igel M, Jensen PB, Tornqvist H, Joost HG et al. Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm Metab Res 1996; 28: 690–693.

    Article  CAS  Google Scholar 

  18. Orci L, Cook WS, Ravazzola M, Wang MY, Park BH, Montesano R et al. Rapid transformation of white adipocytes into fat-oxidizing machines. Proc Natl Acad Sci USA 2004; 101: 2058–2063.

    Article  CAS  Google Scholar 

  19. Waters KM, Miller CW, Ntambi JM . Localization of a negative thyroid hormone-response region in hepatic stearoyl-CoA desaturase gene 1. Biochem Biophys Res Commun 1997; 233: 838–843.

    Article  CAS  Google Scholar 

  20. Liu YY, Brent GA . Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends Endocrinol Metab 2010; 21: 166–173.

    Article  CAS  Google Scholar 

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Acknowledgements

We greatly appreciate the technical assistance of Gerard Pardo, Oscar Rovira and Roser Rodriguez (Unit of Diabetes, Endocrinology and Nutrition (UDEN), Institut d’Investigació Biomèdica de Girona (IdIBGi) and Hospital Universitari de Girona Dr Josep Trueta). This work was supported by research grants from the Ministerio de Educación y Ciencia (SAF2008-02073) and the Instituto de Salud Carlos III (ISCIIIRETIC RD06, CIBERObN), COST Action BM0602 and by the Ministry of Education of the Czech Republic (Research project No. MSM0021622413 and OC08007).

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Correspondence to J M Fernández-Real.

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The contents of this manuscript have not been copyrighted or published previously. There are no directly related manuscripts or abstracts, published or unpublished, by one or more authors of this manuscript. The contents of this manuscript are not now under consideration for publication elsewhere. Neither the submitted manuscript nor any similar manuscript, in whole or in part, will be copyrighted, submitted or published elsewhere while the Journal is under consideration.

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Ortega, F., Jílková, Z., Moreno-Navarrete, J. et al. Type I iodothyronine 5′-deiodinase mRNA and activity is increased in adipose tissue of obese subjects. Int J Obes 36, 320–324 (2012). https://doi.org/10.1038/ijo.2011.101

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