Hormonal Regulation of Leptin, Resistin, and Plasminogen Activator Inhibitor-1 Gene Expression in 3T3-L1 Adipocytes

  • Lee, Hyun-Jung (Department of Food and Nutritional Sciences, Ewha Womans University) ;
  • Kim, Yang-Ha (Department of Food and Nutritional Sciences, Ewha Womans University)
  • Published : 2004.12.01


Leptin, resisitn and PAI-1 (plasminogen activator inhibitor-1) are synthesized and secreted by rodent fat cells and recently postulated to be an important link to obesity. This study was conducted to characterize the hormonal regulation of leptin, resistin, and PAI-1 gene expression in the 3T3-L1 adipocytes. The cells were treated with 0.5 $\mu$M insulin, 1 $\mu$M dexamethasone (Dex), or 0.05 $\mu$M triiodothyronine (T3) for 72 hours. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. The mRNA level of the leptin-producing ob gene was significantly increased by insulin, Dex, and T3 by 3.2-, 3.1- and 2.7-fold, respectively, compared to the control (p < 0.05). The level of resistin mRNA was increased by insulin, Dex, and T3 by 2.7-, 2.5- and 2-fold, respectively, compared to the control (p < 0.05). Likewise, the level of PAI-1 mRNA was significantly increased by insulin, Dex, and T3 compared to the control (p < 0.05). Taken together, our results suggest that insulin, Dex, and T3 may regulate the gene expression of leptin, resistin, and PAI-1 in 3T3-L1 adipocytes.


  1. Halleux CM, Declerck PJ, Tran SL, Detry R, Brichard SM. 1999. Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines. J Clin Endocrinol Metab 84: 4097-4105
  2. Trayhurn P, Beattie JH. 2001. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 60: 329-339
  3. Zhang Y, Proence R, Maffel M, Barone M, Leopold L, Frledman JM. 1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425-432
  4. Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, Hale J, Hoffmann J, Hsiung HM, Kriauciunas A. 1995. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 377: 530-532
  5. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabionowitz D, Lallone RL, Burley SK, Friedman JM. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269: 543-546
  6. Kanu A, Fain JN, Bahouth SW, Cowan GS Jr. 2003. Regulation of leptin release by insulin, glucocorticoids, G(i)- coupled receptor agonists, and pertussis toxin in adipocytes and adipose tissue explants from obese humans in primary culture. Metabolism 52: 60-66
  7. Lee KN, Jeong IC, Lee SJ, Oh SH, Cho MY 2001. Regulation of leptin gene expression by insulin and growth hormone in mouse adipocytes. Exp Mol Med 33: 234-239
  8. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. 1995. Effect of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540-543
  9. Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, Lazar MA. 2001. A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci USA 98: 502-506
  10. Kim KH, Lee K, Moon YS, Sul HS. 2001. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276: 11252-11256
  11. Juhan Vague I, Alessi MC. 1997. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 78: 656-660
  12. Sawdey S, Loskutoff DJ. 1991. Regulation of murine type 1 plasminogen activity inhibitor (PAI-1) gene expression in vivo. Tissue specificity and induction by lipolysaccharide, tumor necrosis factor and transforming growth factor b. J Clin Invest 8: 1346-1353
  13. Lee H, Yang J, Kim Y, Kim Y. 2003. Nutritional regulation of plasminogen activator inhibitor-1, leptin and resistin gene expression in obese mouse. Nutr Sci 6: 73-77
  14. Chomczynski P, Sacchi N. 1987. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol- cholroform extraction. Anal Biochem 162: 156-159
  15. Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, Lowell BB, Spiegelman BM. 1998. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 101: 1-9
  16. Yoshida T, Monkawa T, Hayashi M, Saruta T. 1997. Regulation of expression of leptin mRNA and secretion of leptin by thyroid hormone in 3T3-L1 adipocytes. Biochem Biophys Res Commun 232: 822-826
  17. Medina-Gomez G, Calvo RM, Obregon MJ. 2004. T3 and Triac inhibit leptin secretion and expression in brown and white rat adipocytes. Biochim Biophys Acta 1682: 38-47
  18. Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M, Onishi Y, Ono H, Inukai K, Abe M, Fukushima Y, Kikuchi M, Oka Y, Asano T. 2002. Hormonal regulation of resistion expression in 3T3-L1 and mouse adipose cells. Diabetes 51: 1737-1744
  19. Nogueiras R, Gualillo O, Caminos JE, Casanueva FF, Dieguez C. 2003. Regulation of resistin by gonadal, thyroid hormone, and nutritional status. Obes Res 11: 408- 414
  20. Crandall DL, Busler DE, McHendry-Rinde B, Groeling TM, Kral JG. 2000. Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1. J Clin Endocrinol Metab 85: 2609-2614
  21. Morgange PE, Lijnen HR, Alessi MC, Kope F, Collen D, Juhan-Vague I. 2000. Influence of PAI-1 in adipose tissue growth and metabolic parameters in a murine model of diet-induced obesity. Arterioscler Thromb Vasc Biol 20: 1150-1154
  22. Hekman CM, Loskutoff DJ. 1985. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 260: 11581-11587
  23. Nordt TK, Sawa H, Fujii S, Sobel BE. 1995. Introduction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and insulin in vivo. Circulation 91: 764-770
  24. Kooistra T, Bosma PJ, Tons HA, van den Berg AP, Meyer P, Princen HM. 1989. Plasminogen activator inhibitor 1: biosynthesis and mRNA level are increased by insulin in cultured human hepatocytes. Thromb Heamost 62: 723- 728
  25. Samad F, Loskutoff DJ. 1996. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med 2: 568-582
  26. Eriksson P, Reynisdottir S, Lonnqvist F, Stemme V, Hamsten A, Arner P. 1998. Adipose tissue secretion of plasminogen activator inhibitor-1 an non-obese and obese individuals. Diabetologia 41: 65-71
  27. Heaton JH, Nebes VL, O'bell LG, Morris SM Jr, Gelehrter TD. 1989. Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activatorm inhibitor gene expression in primary cultures of rat hepatocytes. Mol Endocrinol 3: 185-192
  28. Wahrenberg H, Wennlund A, Hoffstedt J. 2002. 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 146: 607-611