Skip to main content

AdipoR1 and AdipoR2 gene expression are regulated by thyroid hormones in adipose tissue

Abstract

The aim of this study was to examine whether the relative gene expression of AdipoR1 and AdipoR2 in rat adipose tissue is altered by thyroid hormones, and whether this might relate to their circulating thyroid hormones and adiponectin levels. Hyper- and hypothyroidism were induced by daily oral administration of levothyroxine and methimazole in rats, respectively, over a 42 days period. Real-time PCR analysis was performed to evaluate the changes in AdipoR1 and AdipoR2 mRNA levels in the adipose tissue on days 15, 28, 42, and also 2 weeks after the cessation of treatment. In response to treatment with methimazole, mRNA levels of AdipoR1 and AdipoR2 decreased in the white adipose tissue compared to the euthyroid rats (p < 0.05). This decline was reversible 2 weeks after treatment cessation. The mRNA levels of AdipoR1 and AdipoR2 were increased in the hyperthyroid group of animals compared to euthyroid control (p < 0.05), and its changes were reversible 2 weeks after treatment cessation (P < 0.05). Adiponectin receptors gene expression levels in the adipose tissue of treated animals have positive correlations with thyroid hormones concentrations. Our results suggest that AdipoR1 and AdipoR2 gene expression is regulated by thyroid hormones in hypo- and hyperthyroidism.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA (2001) The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol 280:827–847

    Google Scholar 

  2. Fortuño A, Rodríguez A, Gómez-Ambrosi J, Frühbeck G, Díez J (2003) Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases. J Physiol Biochem 59:51–60

    Article  PubMed  Google Scholar 

  3. Tabandeh MR, Hosseini A, Saeb M, Kafi M, Saeb S (2010) Changes in the gene expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in ovarian follicular cells of dairy cow at different stages of development. Theriogenology 73:659–669

    CAS  Article  PubMed  Google Scholar 

  4. Cesur G, Ozguner F, Yilmaz N, Dundar B (2012) The relationship between ghrelin and adiponectin levels in breast milk and infant serum and growth of infants during early postnatal life. J Physiol Sci 62:185–190

    CAS  Article  PubMed  Google Scholar 

  5. Berg AH, Combs TP, Scherer PE (2002) ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84–89

    CAS  Article  PubMed  Google Scholar 

  6. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolitic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98:2005–2010

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Pérez-Echarri N, Pérez-Matute P, Martínez JA, Marti A, Moreno-Aliaga MJ (2005) Serum and gene expression levels of leptin and adiponectin in rats susceptible or resistant to dietinduced obesity. J Physio Biochem 61:333–342

    Article  Google Scholar 

  8. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T (2003) Globular adiponectin protected ob/ob mice from diabetes and apoE-deficient mice from atherosclerosis. J Biol Chem 278:2461–2468

    CAS  Article  PubMed  Google Scholar 

  9. Kadowaki T, Yamauchi T, Kubota N (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295

    CAS  Article  PubMed  Google Scholar 

  11. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N, Terauchi Y, Froguel P, Nakae J, Kasuga M, Accili D, Tobe K, Ueki K, Nagai R, Kadowaki T (2004) Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 279:30817–30822

    CAS  Article  PubMed  Google Scholar 

  12. Fischer-Posovszky P, Wabitsch M, Hochberg Z (2007) Endocrinology of adipose tissue—an update. Horm Metab Res 39:314–321

    CAS  Article  PubMed  Google Scholar 

  13. Iglesias P, Alvarez FP, Codoceo R, Diez JJ (2003) Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function. Clin Endocrinol 59:621–629

    CAS  Article  Google Scholar 

  14. Aragao CN, Souza LL, Cabanelas A, Oliveira KJ, Pazos-Moura CC (2007) Effect of experimental hypo- and hyperthyroidism on serum adiponectin. Metabolism 56:6–11

    CAS  Article  PubMed  Google Scholar 

  15. Saito T, Kawano T, Saito T, Ikoma A, Namai K, Tamemoto H, Kawakami M, Ishikawa S (2005) Elevation of serum adiponectin levels in Basedow disease. Metabolism 54:1461–1466

    CAS  Article  PubMed  Google Scholar 

  16. Sieminska L, Niedziolka D, Pillich A, Kos-Kudla B, Marek B, Nowak M, Borgiel-Marek H (2008) Serum concentrations of adiponectin and resistin in hyperthyroid Graves’ disease patients. J Endocrinol Invest 31:745–749

    CAS  Article  PubMed  Google Scholar 

  17. Seifi S, Tabandeh MR, Nazifi S, Saeb M, Shirian S, Sarkoohi P (2012) Regulation of adiponectin gene expression in adipose tissue by thyroid hormones. J Physiol Biochem 68:193–203

    CAS  Article  PubMed  Google Scholar 

  18. Santini F, Marsili A, Mammoli C, Valeriano R, Scartabelli G, Pelosini C, Giannetti M, Centoni R, Vitti P, Pinchera A (2004) Serum concentrations of adiponectin and leptin in patients with thyroid dysfunctions. J Endocrinol Invest 27:5–7

    Article  Google Scholar 

  19. Pontikides N, Krassas GE (2007) Basic endocrine products of adipose tissue in states of thyroid dysfunction. Thyroid 17:421–431

    CAS  Article  PubMed  Google Scholar 

  20. Botella-Carretero JI, Alvarez-Blasco F, Sancho J, Escobar-Morreale HF (2006) Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal. Thyroid 16:397–402

    CAS  Article  PubMed  Google Scholar 

  21. Cabanelas A, Cordeiro A, Almeida NAS, de Paula GSM, Coelho VM, Ortiga-Carvalho TM, Pazos-Moura CC (2010) Effect of triiodothyronine on adiponectin expression and leptin release by white adipose tissue of normal rats. Horm Metab Res 42:254–260

    CAS  Article  PubMed  Google Scholar 

  22. Pfaffl MW (2001) A new mathemathical model for relative quantitation in real-time RT-PCR. Nucl Acid Res 29:45

    Article  Google Scholar 

  23. Luvizotto RAM, Síbio MT, Olímpio RMC, Nascimento AF, Lima-Leopoldo AP, Leopoldo AS, Padovani CR, Cicogna AC, Nogueira CR (2011) Supraphysiological triiodothyronine doses diminish leptin and adiponectin gene expression, but do not alter resistin expression in calorie restricted obese rats. Horm Metab Res 43:452–457

    CAS  Article  PubMed  Google Scholar 

  24. Oppenheimer JH, Silva E, Schwartz HL, Surks M (1977) Stimulation of hepatic mitochondrial α-glycerophospate dehydrogenase and malic enzyme by, l-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated. J Clin Invest 59:517–527

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Mracek T, Jesina P, Krivakova P, Bolehovska R, Cervinkova Z, Drahota Z, Houstek J (2005) Time course of hormonal induction of mitochondrial glycerophosphate dehydrogenase biogenesis in rat liver. Biochim Biophys Acta 1726:217–223

    CAS  Article  PubMed  Google Scholar 

  26. Agdeppa D, Macaron C, Mallik T, Schnuda ND (1979) Plasma high density lipoprotein cholesterol in thyroid disease. J Clin Endocrinol Metab 49:726–729

    CAS  Article  PubMed  Google Scholar 

  27. Duntas LH (2002) Thyroid disease and lipids. Thyroid 12:287–293

    CAS  Article  PubMed  Google Scholar 

  28. Tan GD, Debard C, Funahashi T, Humphreys SM, Matsuzawa Y, Frayn KN, Karpe F, Vidal H (2005) Changes in adiponectin receptor expression in muscle and adipose tissue of type 2 diabetic patients during rosiglitazone therapy. Diabetologia 48:1585–1589

    CAS  Article  PubMed  Google Scholar 

  29. Tsuchida A, Yamauchi T, Takekawa S, Hada Y, Ito Y, Mak T, Kadowaki T (2005) Peroxisome proliferators activated receptor (PPAR) alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPAR alpha, PPAR gamma, and their combination. Diabetes 54:3358–3370

    CAS  Article  PubMed  Google Scholar 

  30. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13:332–339

    Google Scholar 

  31. Schultz M, Kistorp C, Raymond I, Dimsits J, Tuxen C, Hildebrandt P, Faber J (2011) Cardiovascular events in thyroid disease: a population based. Prospect Study Horm Metab Res 43:653–659

    Google Scholar 

  32. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Nagai R, Kimura S, Kadowaki T, Noda T (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277:25863–25866

    Google Scholar 

  33. Kyriazi E, Tsiotra PC, Boutati E, Ikonomidis I, Fountoulaki K, Maratou E, Lekakis J, Dimitriadis G, Kremastinos DT, Raptis SA (2011) Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages. Horm Metab Res 43:537–544

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was financially supported by the Shahid Chamran University of Ahvaz (Grant No. 89/3/02/44305) and Shiraz University.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mohammad Reza Tabandeh.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Seifi, S., Nazifi, S., Tabandeh, M.R. et al. AdipoR1 and AdipoR2 gene expression are regulated by thyroid hormones in adipose tissue. Mol Cell Biochem 377, 55–63 (2013). https://doi.org/10.1007/s11010-013-1570-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1570-5

Keywords

  • Adiponectin receptors
  • Gene expression
  • Adipose tissue
  • Hypothyroidism
  • Hyperthyroidism