[go: up one dir, main page]

Skip to main content
Log in

Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Clenbuterol, a beta2-adrenergic receptor (β2-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice. We hypothesized that direct actions of a β-adrenergic receptor agonist on adipocytes could trigger the observed apoptotic effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with 10−9 to 10−5 M clenbuterol depending on the experiments. There was no apoptotic effect of clenbuterol both in 3T3-L1 cells and rat primary adipocytes. Adipogenesis monitored by Oil Red O staining and AdipoRed™ assay was modestly decreased by clenbuterol treatment (p < 0.05). In fully differentiated primary adipocytes, clenbuterol increased basal lipolysis compared with the control (p < 0.01). In summary, direct stimulation of β2-AR by clenbuterol does not cause apoptosis in adipocytes, despite a direct lipolytic stimulation and attenuation of adipogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ambati S, Kim HK, Yang JY, Lin J, Della-Fera MA, Baile CA (2007) Effects of leptin on apoptosis and adipogenesis in 3T3-L1 adipocytes. Biochem Pharmacol 73:378–384

    Article  CAS  PubMed  Google Scholar 

  2. Baltensperger K, Karoor V, Paul H, Ruoho A, Czech MP, Malbon CC (1996) The beta-adrenergic receptor is a substrate for insulin receptor tyrosine kinase. J Biol Chem 271:1061–1064

    Article  CAS  PubMed  Google Scholar 

  3. Bamshad M, Aoki VT, Adkison MG, Warren WS, Bartness TJ (1998) Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am J Physiol 275:R291–R299

    CAS  PubMed  Google Scholar 

  4. Burniston JG, Tan LB, Goldspink DF (2005) β2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle. J Appl Physiol 98:1379–1386

    Article  CAS  PubMed  Google Scholar 

  5. Carpéné C, Chalaux E, Lizarbe M, Estrada A, Mora C, Palacin M, Zorzano A, Lafontan M, Testar X (1993) β3-adrenergic receptors are responsible for the adrenergic inhibition of insulin-stimulated glucose transport in rat adipocytes. Biochem J 296:99–105

    PubMed  Google Scholar 

  6. Choi YH, Li C, Page K, Westby A, Della-Fera MA, Lin J, Hartzell DL, Baile CA (2003) Melanocortin receptors mediate leptin effects on feeding and body weight but not adipose apoptosis. Physiol Behav 79:795–801

    Article  CAS  PubMed  Google Scholar 

  7. Cohen B, Barkan D, Levy Y, Goldberg I, Fridman E, Kopolovic J, Rubinstein M (2001) Leptin induces angiopoietin-2 expression in adipose tissues. J Biol Chem 276:7697–7700

    Article  CAS  PubMed  Google Scholar 

  8. Dunbar JC, Hu Y, Lu H (1997) Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 46:2040–2043

    Article  CAS  PubMed  Google Scholar 

  9. Fu YC, Chi CS, Yin SC, Hwang B, Chiu YT, Hsu SL (2004) Norepinephrine induces apoptosis in neonatal rat endothelial cells via down-regulation of Bcl-2 and activation of beta-adrenergic and caspase-2 pathways. Cardiovasc Res 61:143–151

    Article  CAS  PubMed  Google Scholar 

  10. Gullicksen PS, Della-Fera MA, Baile CA (2003) Leptin-induced adipose apoptosis: implications for body weight regulation. Apoptosis 8:327–335

    Article  CAS  PubMed  Google Scholar 

  11. Haque MS, Minokoshi Y, Hamai M, Iwai M, Horiuchi M, Shimazu T (1999) Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes 48:1706–1712

    Article  CAS  PubMed  Google Scholar 

  12. Hausman DB, Park HJ, Hausman GJ (2008) Isolation and culture of preadipocytes from rodent white adipose tissue. Meth Mol Biol 456:201–219

    Article  Google Scholar 

  13. Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest 100:270–278

    Article  CAS  PubMed  Google Scholar 

  14. Hemati N, Ross SE, Erickson RL, Groblewski GE, MacDougald OA (1997) Signaling pathways through which insulin regulates CCAAT/enhancer binding protein alpha (C/EBP alpha) phosphorylation and gene expression in 3T3-L1 adipocytes. Correlation with GLUT4 gene expression. J Biol Chem 272:25913–25919

    Article  CAS  PubMed  Google Scholar 

  15. Hinkle RT, Hodge KM, Cody DB, Sheldon RJ, Kobilka BK, Isfort RJ (2002) Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the β2-adrenergic receptor. Muscle Nerve 25:729–734

    Article  CAS  PubMed  Google Scholar 

  16. Jang M, Mistry A, Swick AG, Romsos DR (2000) Leptin rapidly inhibits hypothalamic neuropeptide Y secretion and stimulates corticotrophin-releasing hormone-secretion in adrenalectomized mice. J Nutr 130:2813–2820

    CAS  PubMed  Google Scholar 

  17. Karoor V, Baltensperger K, Paul H, Czech MP, Malbon MP (1995) Phosphorylation of tyrosyl residues 350/354 of the beta-adrenergic receptor is obligatory for counterregulatory effects of insulin. J Biol Chem 270:25305–25308

    Article  CAS  PubMed  Google Scholar 

  18. Kim HK, Nelson-Dooley C, Della-Fera MA, Yang JY, Zhang WZ, Hartzel DL, Hamrick MW, Baile CA (2006) Genistein decreases food intake body weight and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr 136:409–414

    CAS  PubMed  Google Scholar 

  19. Lin J, Page KA, Della-Fera MA, Baile CA (2004) Evaluation of adipocyte apoptosis by laser scanning cytometry. Int J Obes 28:1535–1540

    Article  CAS  Google Scholar 

  20. Linquist JM, Rehnmark S (1998) Ambient temperature regulation of apoptosis in brown tissue Erk1/2 promotes norepinephrine-dependent cell survival. J Biol Chem 273(46):30147–30156

    Article  Google Scholar 

  21. Liu CY, Boyer JL, Mills SE (1989) Acute effects of beta-adrenergic agonists on porcine adipocyte metabolism in vitro. J Anim Sci 67:2930–2936

    CAS  PubMed  Google Scholar 

  22. Mills SE, Spurlock ME, Smith DJ (2003) Beta-adrenergic receptor subtypes that mediate ractopamine stimulation of lipolysis. J Anim Sci 81:662–668

    CAS  PubMed  Google Scholar 

  23. Page KA, Hartzell DL, Li C, Westby AL, Della-Fera MA, Azain MJ, Pringle TD, Baile CA (2004) β-Adrenergic receptor agonists increase apoptosis of adipose tissue in mice. Domest Anim Endocrinol 26:23–31

    Article  CAS  PubMed  Google Scholar 

  24. Parr MK, Koehler K, Geyer H, Guddat S, Schanzer W (2008) Clenbuterol marketed as dietary supplement. Biomed Chromatogr 22:298–300

    Article  CAS  PubMed  Google Scholar 

  25. Qian H, Azain MJ, Compton MH, Hartzell DL, Hausman GJ, Baile CA (1998) Brain administration of leptin causes deletion of adipocytes by apoptosis. Endocrinology 139:791–794

    Article  CAS  PubMed  Google Scholar 

  26. Satoh N, Ogawa Y, Katsuura G, Numata Y, Tsuji T, Hayase M, Ebihara K, Masuzaki H, Hosoda K, Yoshimasa Y, Nakao K (1999) Sympathetic activation of leptin via the ventromedial hypothalamus leptin-induced increase in catecholamine secretion. Diabetes 48:1787–1793

    Article  CAS  PubMed  Google Scholar 

  27. Singh K, Xiao L, Remondino A, Sawyer DB, Colucci WS (2001) Adrenergic regulation of cardiac myocyte apoptosis. J Cell Physiol 189:257–265

    Article  CAS  PubMed  Google Scholar 

  28. Sorisky A, Magun R, Gagnon AM (2000) Adipose cell apoptosis death in the energy depot. Int J Obes Relat Metab Disord 24:S3–S7

    Article  CAS  PubMed  Google Scholar 

  29. Suryaan A, Hu CY (1993) Effect of serum on differentiation of porcine adipose stromal-vascular cells in primary culture. Comp Biochem Physiol 105:485–492

    Article  Google Scholar 

  30. Wang ZW, Zhou YT, Lee Y, Higa M, Kalra SP, Unger RH (1999) Hyperleptinemia depletes fat from denervated fat tissue. Biochem Biophy Res Commun 260:653–657

    Article  CAS  Google Scholar 

  31. Zhang J, He Q, Liu QY, Guo W, Deng XM, Zhang WW, Hu XX, Li N (2007) Differential gene expression profile in pig adipose tissue treated with/without clenbuterol. BMC Genomics 26:433

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported in part by the Georgia Research Alliance Eminent Scholar endowment held by CA Baile.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clifton A. Baile.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, HK., Della-Fera, M.A., Hausman, D.B. et al. Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes. J Physiol Biochem 66, 197–203 (2010). https://doi.org/10.1007/s13105-010-0024-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-010-0024-8

Keywords

Navigation