Horm Metab Res 2010; 42(4): 254-260
DOI: 10.1055/s-0029-1246118
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Effect of Triiodothyronine on Adiponectin Expression and Leptin Release by White Adipose Tissue of Normal Rats

A. Cabanelas1 , A. Cordeiro1 , N. A. dos Santos Almeida1 , G. S. Monteiro de Paula1 , V. M. Coelho2 , T. M. Ortiga-Carvalho1 , C. C. Pazos-Moura1
  • 1Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
  • 2Laboratório de Imunofisiologia, Instituto de Ciências Biomédicas Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Further Information

Publication History

received 10.08.2009

accepted 10.12.2009

Publication Date:
21 January 2010 (online)

Abstract

Previous studies have shown that alterations in thyroid status may lead to changes in serum leptin and adiponectin, both in humans and rodents. The mechanisms, especially for adiponectin, are unclear. In the present study, we investigated the effect of triiodothyronine (T3) on the expression of adiponectin mRNA and the release of leptin and adiponectin by white adipose tissue (WAT) explants obtained from epididymal (visceral) or inguinal (subcutaneous) depots from normal rats. We also analyzed the effects of other known regulators of adiponectin and leptin release, such as rosiglitazone and dexamethasone. T3 acted directly at rat WAT explants in a depot-specific manner and in a unique fashion to each hormone. T3 was able to inhibit leptin release only by epididymal explants, and to reduce adiponectin mRNA expression only in inguinal explants. However, T3 was incapable of modifying adiponectin release by both explants. Additionally, rosiglitazone exhibited an inhibitory effect on adiponectin release by both WAT explants, even though adiponectin mRNA was importantly upregulated only in inguinal explants. Rosiglitazone acted as an inhibitor of leptin release by both studied fat depots, while only epididymal explants responded to the stimulatory effect of dexamethasone on leptin release. Therefore, the present model of isolated rat white adipose tissue explants highlights the fact that the regulation of hormonal production by white adipose tissue depends on the type of depot and its anatomical location. In this context, our results show for the first time a potential inhibitory effect of T3 on adiponectin mRNA expression specifically on WAT from a subcutaneous depot.

References

  • 1 Ahima RS. Adipose tissue as an endocrine organ.  Obesity. 2006;  14 ((Suppl 5)) 242S-249S
  • 2 Oetting A, Yen PM. New insights into thyroid hormone action.  Best Pract Res Clin Endocrinol Metab. 2007;  21 193-208
  • 3 Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting.  Nature. 1996;  382 250-252
  • 4 Légrándi G, Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus.  Endocrinology. 1997;  138 2569-2576
  • 5 Nillni EA, Vaslet C, Harris M, Hollenberg A, Bjørbak C, Flier JS. Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways.  J Biol Chem. 2000;  275 36124-36133
  • 6 Seoane LM, Carro E, Tovar S, Casanueva FF, Dieguez C. Regulation of in vivo TSH secretion by leptin.  Reg Pep. 2000;  92 25-29
  • 7 Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjøorbaek C, Elmquist JK, Flier JS, Hollenberg AN. Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling.  J Clin Invest. 2001;  107 111-120
  • 8 Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC. The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies.  J Endocrinol. 2002;  174 121-125
  • 9 Hoyda TD, Samson WK, Ferguson AV. Adiponectin depolarizes parvocellular paraventricular nucleus neurons controlling neuroendocrine and autonomic function.  Endocrinology. 2009;  150 832-840
  • 10 Escobar-Morreale HF, Del Rey FE, Escobar GM. Thyroid hormones influence serum leptin concentrations in the rat.  Endocrinology. 1997;  138 4485-4488
  • 11 Zimmermann-Belsing T, Brabant G, Holst JJ, Feldt-Rasmussen U. Circulating leptin and thyroid dysfunction.  Eur J Endocrinol. 2003;  149 257-271
  • 12 Kokkinos A, Mourouzis I, Kyriaki D, Pantos C, Katsilambros N, Cokkinos DV. Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone.  Endocr. 2007;  32 30-32
  • 13 Medina-Gomes G, Calvo RM, Obregón MJ. T3 and Triac inhibit leptin secretion and expression in brown and white rat adipocytes.  Biochim Biophys Acta. 2004;  1682 38-47
  • 14 Fain JN, Bahouth SW. Effect of tri-iodothyronine on leptin release and leptin nRNA accumulation in rat adipose tissue.  Biochem J. 1998;  332 361-366
  • 15 Aragão CN, Souza LL, Cabanelas A, Oliveira KJ, Pazos-Moura CC. Effect of experimental hypo- and hyperthyroidism on serum adiponectin.  Metabolism. 2007;  56 6-11
  • 16 Fujimoto N, Matsuo N, Sumiyoshi H, Yamaguchi K, Saikawa T, Yoshimatsu H, Yoshioka H. Adiponectin is expressed in the brown adipose tissue and surrounding immature tissues in mouse embryos.  Biochim Biophys Acta. 2005;  1731 1-12
  • 17 Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3–L1 adipocytes.  Biochem Biophys Res Comm. 2002;  290 1084-1089
  • 18 Corbetta S, Englaro P, Giambona S, Persani L, Blum WF, Beck-Peccoz P. Lack of effects of circulating thyroid hormone levels on serum leptin concentrations.  Eur J Endocrinol. 1997;  37 659-663
  • 19 Sreenan S, Caro JF, Refetoff S. Thyroid dysfunction is not associated with alterations in serum leptin levels.  Thyroid. 1997;  7 407-409
  • 20 Valcavi R, Zini M, Peino R, Casanueva FF, Dieguez C. Influence of thyroid status on serum immunoreactive leptin levels.  J Clin Endocrinol Metab. 1997;  82 1632-1634
  • 21 Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism.  J Endocrinol. 1998;  157 75-79
  • 22 Wahrenberg H, Wennlund A, Hoffstedt J. Increased adipose tissue secretion of interleukin-6, but not of leptin, plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves' hyperthyroidism.  Eur J Endocrinol. 2002;  146 607-611
  • 23 Pinkney JH, Goodrick SJ, Katz J, Johnson AB, Lightman SL, Coppack SW, Mohamed-Ali V. Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects.  Clin Endocrinol (Oxf). 1998;  49 583-588
  • 24 Matsubara M, Yoshizawa T, Morioka T, Katayose S. Serum leptin and lipids in patients with thyroid dysfunction.  J Atheroscler Thromb. 2000;  7 50-54
  • 25 Iglesias P, Fidalgo PA, Codoceo R, Codoceo R, Díez JJ. Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function.  Clin Endocrinol (Oxf). 2003;  59 621-629
  • 26 Nakamura T, Nagasaka S, Ishikawa S, Hayashi H, Saito T, Kusaka I, Higashiyama M, Saito T. Association of hyperthyroidism with serum leptin levels.  Metabolism. 2000;  49 1285-1288
  • 27 Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T. Serum leptin concentrations in patients with thyroid disorders.  Clin Endocrinol (Oxf). 1998;  48 299-302
  • 28 Hsieh CJ, Wang PW, Wang ST, Liu RT, Tung SC, Chien WY, Lu YC, Chen JF, Chen CH, Kuo MC. Serum leptin concentrations of patients with sequential thyroid function changes.  Clin Endocrinol (Oxf). 2002;  57 29-34
  • 29 Saito T, Kawano T, Saito T, Ikoma A, Namai K, Tamemoto H, Kawakami M, Ishikawa SE. Elevation of serum adiponectin levels in Basedow disease.  Metab Clin Experiment. 2005;  54 1461-1466
  • 30 Yaturu S, Prado S, Grimes SR. Changes in adipocyte hormones leptin, resistin, and adiponectin in thyroid dysfunction.  J Cell Biochem. 2004;  93 491-496
  • 31 Mineo HA, Oda C, Chiji H, Kawada T, Shimizu K, Taira T. Thiazolidinediones exhibit different effects on preadipocytes isolated from rat mesenteric fat tissue and cell line 3T3-L1 cells derived from mice.  Cell Biol Int. 2007;  31 703-710
  • 32 Phillips SA, Ciaraldi TP, Oh DK, Savu MK, Henry RR. Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue.  Am J Physiol Endocrinol Metab. 2008;  295 842-850
  • 33 Fain JN, Buehrer B, Tichansky DS, Madan AK. Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue.  Int J Obes. 2008;  32 429-435
  • 34 Laviola L, Perrini S, Cignarelli A, Natalicchio A, Leonardini A, De Stefano F, Cuscito M, De Fazio M, Memeo V, Neri V, Cignarelli M, Giorgino R, Giorgino F. Insulin signaling in human visceral and subcutaneous adipose tissue in vivo.  Diabetes. 2006;  55 952-961
  • 35 Lefebvre AM, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, Vidal H. Depot-specific differences in adipose tissue gene expression in lean and obese subjects.  Diabetes. 1998;  47 98-103
  • 36 Vab Harmelen V, Reynisdottir S, Eriksson P, Thörne A, Hoffstedt J, Lönnqvist F, Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women.  Diabetes. 1998;  47 913-917
  • 37 Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans.  Endocrinology. 2004;  145 2273-2282
  • 38 Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato EL, Barbot DJ, Rosato FE, Goldstein BJ. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone.  J Clin Endocrinol Metab. 2002;  87 5662-5667
  • 39 Delporte ML, Funahashi T, Takahashi M, Matsuzawa Y, Brichard SM. Pre- and post-translational negative effect of beta-adrenoceptor agonist on adiponectin secretion: in vitro and in vivo studies.  Biochem J. 2002;  367 677-685
  • 40 Altomonte J, Harbaran S, Richter A, Dong H. Fat depot-specific expression of adiponectin is impaired in Zucker fatty rats.  Metabolism. 2003;  52 958-963
  • 41 Atzmon G, Yang XM, Muzumdar R, Ma XH, Gabriely I, Barzilai N. Differential Gene Expression Between Visceral and Subcutaneous Fat Depots.  Horm Metab Res. 2002;  34 622-628
  • 42 Oliver P, Picó C, Palou A. Ontogenesis of leptin expression in different adiposetissue depots in the rat.  Pflügers Arch – Eur J Physiol. 2001;  442 383-390
  • 43 Wajchenberg B L. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome.  Endocr Rev. 2000;  21 697-738
  • 44 Samuels HH, Stanley F, Casanova J. Depletion of L-3,5,3-triiodothyronine and l-thyroxine in euthyroid calf serum for use in cell culture studies of action of thyroid hormone.  Endocrinology. 1979;  105 80-85
  • 45 Machado DS, Sabeta A, Santiago LA, Sidhaye AR, Chiamolera MI, Ortiga-Carvalho TM, Wondisford FE. A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo.  Proc Natl Acad Sci U S A. 2009;  106 9441-9446
  • 46 Yoda M, Nakano Y, Tobe T, Shioda S, Choi-Miura NH, Tomita M. Characterization of mouse GBP28 and its induction by exposure to cold.  Int J Obes. 2001;  25 75-83
  • 47 Quinn CE, Hamilton PK, Lockhart CJ, McVeigh GE. Thiazolidinediones: effects on insulin resistance and the cardiovascular system.  Brit J Pharmacol. 2008;  153 636-645
  • 48 Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y. PPAR ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.  Diabetes. 2001;  50 2094-2099
  • 49 Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors.  Diabetes. 2003;  52 1655-1663
  • 50 Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, Wagner JA, Wu M, Knopps A, Xiang AH, Utzschneider KM, Kahn SE, Olefsky JM, Buchanan TA, Scherer PE. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulinsensitivity.  J Biol Chem. 2004;  279 12152-12162
  • 51 Tonelli J, Li W, Kishore P, Pajvani UB, Kwon E, Weaver C, Scherer PE, Hawkins M. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in Type 2 Diabetes.  Diabetes. 2004;  53 1621-1629
  • 52 Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L, Scherer PE. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor agonists.  J Biol Chem. 2006;  281 2654-2660
  • 53 Viengchareun S, Zennaro MC, Lê Tallec LP. Brown adipocytes are novel sites of expression and regulation of adiponectin and resistin.  Fed Eur Biochem Soc Lett. 2002;  532 345-350
  • 54 Rasouli N, Yao-Borengasser A, Miles LM, Elbein SC, Kern PA. Increased plasma adiponectin in response to pioglitazone does not result from increased gene expression.  Am J Physiol Endocrinol Metab. 2006;  290 E42-E46
  • 55 Combs TP, Wagner JA, Berger J, Doebber T, Wang WJ, Zhang BB, Tanen M, Berg AH, O'Rahilly S, Savage DB, Chatterjee K, Weiss S, Larson PJ, Gottesdiener KM, Gertz BJ, Charron MJ, Scherer PE, Moller DE. Induction of adipocyte complement-related protein of 30 kilodaltons by PPARgamma agonists: a potential mechanism of insulin sensitization.  Endocrinology. 2002;  143 998-1007
  • 56 Inokuchi T, Tsutsumi Z, Takahashi S, Ka T, Yamamoto A, Moriwaki Y, Masuzaki H, Yamamoto T. Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro.  Horm Metab Res. 2009;  41 327-332
  • 57 Klimcakova E, Moro C, Mazzucotelli A, Lolmède K, Viguerie N, Galitzky J, Stich V, Langin D. Profiling of adipokines secreted from human subcutaneous adipose tissue in response to PPAR agonists.  Biochem Bioph Res Comm. 2007;  358 897-902
  • 58 De Vos P, Saladin R, Auwerx J, Staels B. Induction of ob gene expression by corticosteroids is accompanied by body weight loss and reduced food intake.  J Biol Chem. 1995;  270 15958-15961
  • 59 Murakami T, Iida M, Shima K. Dexamethasone regulates obese expression in isolated rat adipocytes.  Biochem Biophys Res Comm. 1995;  214 126-127
  • 60 Slieker LJ, Sloop KW, Surface PL, Kriauciunas A, LaQuier F, Manetta J, Bue-Valleskey J, Stephens TW. Regulation of ob mRNA and protein by glucocorticoids and cAMP.  J Biol Chem. 1996;  271 5301-5304
  • 61 Halleux CM, Takahashi M, Delporte ML, Detry R, Funahashi T, Matsuzawa Y, Brichard SM. Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue.  Biochem Biophys Res Comm. 2001;  288 1102-1107
  • 62 Degawa-Yamauchi M, Moss KA, Bovenkerk JE, Shankar SS, Morrison CL, Lelliott CJ, Vidal-Puig A, Jones R, Considine RV. Regulation of Adiponectin expression in human adipocytes: effect of adiposity, glucocorticoids, and tumor necrosis factor alpha.  Obes Res. 2005;  13 662-669
  • 63 Patel JV, Cummings DE, Girod JP, Mascarenhas AV, Hughes EA, Gupta M, Lip GY, Reddy S, Brotman DJ. Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment.  J Negat Results Biomed. 2006;  11 14

Correspondence

C. C. Pazos-Moura

Instituto de Biofísica Carlos

Chagas Filho

Universidade Federal do Rio de Janeiro

CCS, Bloco G

21941–902 Rio de Janeiro

Brazil

Phone: +55/21/2562 6535

Fax: +55/21/2808 193

Email: cpazosm@biof.ufrj.br