Molecular and Cellular Biochemistry

, Volume 221, Issue 1–2, pp 109–115 | Cite as

Effect of oleoyl‐esterone treatment on the expression of β1- β2‐ and β3‐adrenoreceptors in rat adiopose tissues

  • Cristina Cabot
  • Maria del Mar Grasa
  • José Antonio Fernández‐López
  • Marià Alemany


Adult female rats received a constant i.v. infusion of oleoyl‐estrone (3.5 μmol/kg day) in a lipidic suspension for 14 days. On days 0 (no treatment), 3, 6, 10 and 14, as well as on day 14 for controls (receiving only the lipid); the rats were killed and the expression of the β1‐, β2‐ and β3‐adrenoceptor genes, in brown adipose tissue and in subcutaneous and periovaric white adipose tissue, were measured by RNA protection assay, and compared with that of cyclophyllin. The β3‐adrenoceptor was the most expressed in all adipose tissues, whereas β2 was the less expressed in brown adipose tissue. Oleoyl‐estrone significantly, but moderately, increased the expression of β‐adrenoceptors in the three adipose tissues: β1 increased in subcutaneous, β2 and β3 in periovaric and β3 in brown adipose tissue. Oleoyl‐estrone also decreased β3 expression in subcutaneous white adipose tissue. On day 10, adipocytes isolated from periovaric white adipose tissue of oleoyl‐estrone‐treated rats showed higher cAMP response to an isoproterenol challenge than the controls. The mechanism by which oleoyl‐estrone elicits the wasting of fat reserves could be mediated by adrenergic pathways, at least in part.

β1‐adrenoceptors β2adrenoceptors β3‐adrenoceptors oleoyl‐estrone cAMP white adipose tissue brown adipose tissue BAT WAT 


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  1. 1.
    Sanchis D, Balada F, Grasa MM, Virgili J, Peinado J, Monserrat C, Fernández-López JA, Remesar X, Alemany M: Oleoyl-estrone induces the loss of body fat in rats. Int J Obesity 20: 588–594, 1996Google Scholar
  2. 2.
    Balada F, Sanchis D, Grasa MM, Virgili J, Estruch J, Fernández-López JA, Remesar X, Alemany M: Effect of the slimming agent oleoylestrone in liposomes on the body weight of Zucker obese rats. Int J Obesity 21: 789–895, 1997CrossRefGoogle Scholar
  3. 3.
    Grasa MM, Esteve M, Masanés RM, Yubero P, Blay M, López-Martí J, Cabot C, Vilà R, Fernández-López JA, Remesar X, Alemany M: Oral gavage of oleoyl-estrone has a stronger effect on body fat in male Zucker rats than in female. Diabet Obes Metab, 2001 (in press)Google Scholar
  4. 4.
    Virgili J, Casals I, Peinado J, Esteve M, Julve J, Fernández-López JA, Remesar X, Alemany M: Distribution of oleoyl-estrone in rat plasma lipoproteins. Horm Metab Res 31: 597–601, 1999CrossRefPubMedGoogle Scholar
  5. 5.
    Esteve M, Virgili J, Aguilar H, Balada F, Fernández-López JA, Remesar X, Alemany M: Leptin enhances the synthesis of oleoyl-estrone from estrone in white adipose tissue. Eur J Nutr 38: 99–104, 1999CrossRefPubMedGoogle Scholar
  6. 6.
    Adán C, Cabot C, Esteve M., Grasa MM, Masanés R, Vilà R, Estruch J, Fernández-López JA, Remesar X, Alemany M: Oleoyl-estrone treatment affects the ponderostat setting differently in lean and in obese Zucker rats. Int J Obesity 22: 366–373, 1999CrossRefGoogle Scholar
  7. 7.
    Sanchis D, Adán C, Ardévol A, Grasa MM, Cabot C, Balada F, Vilà R, Estruch J, Puerta ML, Fernández-López JA, Remesar X, Alemany M: Short-term treatment with oleoyl-estrone in liposomes (Merlin-2) strongly reduces the expression of the ob gene in young rats. Biochem J 326: 357–360, 1997CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yubero P, Graupera M, Fernández-López JA, Remesar X, Alemany M: Estimulación directa por la oleoil-estrona de la lipolisis en células adiposas humanas aisladas. Nutr Obes 2(suppl 1): (abstr) 15, 1999Google Scholar
  9. 9.
    Sanchis D, Balada F, Picó C, Grasa MM, Virgili J, Farrerons C, Palou A, Fernández-López JA, Remesar X, Alemany M: Rats receiving the slimming agent oleoyl-estrone in liposomes Merlin-2; decrease food intake but maintain thermogenesis. Arch Physiol Biochem 105: 663–672, 1997CrossRefPubMedGoogle Scholar
  10. 10.
    Okuda H, Morimoto C, Tsujita T: β-adrenergic receptors in rat fat cells and their relationship with lipolysis. J Biochem 119: 852–856, 1996CrossRefPubMedGoogle Scholar
  11. 11.
    Faintrenie G, Géloën A: α-1 adrenergic regulation of lactate production by white adipocytes. J Pharmacol Exp Ther 277: 235–238, 1996PubMedGoogle Scholar
  12. 12.
    Flier JS: The adipocyte: Storage depot or node on the energy information superhighway? Cell 80: 15–18, 1995CrossRefPubMedGoogle Scholar
  13. 13.
    Blum WF: Leptin: The voice of the adipose tissue. Horm Res 48(suppl 4): 2–8, 1997CrossRefPubMedGoogle Scholar
  14. 14.
    Langin D, Portillo MP, Saulnier-Blanche JS, Lafontan M: Coexistence of three β-adrenoceptor subtypes in white fat cells of various mammalian species. Eur J Pharmacol 199: 291–301, 1991CrossRefPubMedGoogle Scholar
  15. 15.
    Tavernier G, Galitzky J, Valet P, Remaury A, Bouloumie A, Lafontan M, Langin D: Molecular mechanisms underlying regional variations of catecholamine-induced lipolysis in rat adipocytes. Am J Physiol 268: E1135–E1142, 1995PubMedGoogle Scholar
  16. 16.
    Bengtsson T: β-Adrenergic receptors: genes and expression. PhD thesis. Stockholm University, 1998Google Scholar
  17. 17.
    Liggett SB: Functional properties of the rat human β3-adrenergic receptors: Differential agonist activation of recombinant receptors in Chinese hamster ovary cells. Mol Pharmacol 42: 634–637, 1992PubMedGoogle Scholar
  18. 18.
    Carpéné C, Castan I, Collon P, Galitzky J, Moratinos J, Lafontan M: Adrenergic lipolysis in guinea pig is not a β3-adrenergic response: Comparison with human adipocytes. Am J Physiol 266: R905–R913, 1994PubMedGoogle Scholar
  19. 19.
    McNeel RL, Mersmann HJ: β-adrenergic receptor subtype transcripts in porcine adipose tissue. J Anim Sci 73: 1962–1971, 1995CrossRefPubMedGoogle Scholar
  20. 20.
    Zhao J, Unelius L, Bengtsson B, Cannon B, Nedergaard J: Coexisting β-adrenoceptor subtypes: Significance for thermogenic process in brown fat cells. Am J Physiol 267: C969–C979, 1994PubMedGoogle Scholar
  21. 21.
    Manara L, Croci T, Landi M: β3-adrenoceptors and intestinal motility. Fund Clin Pharmacol 9: 332–342, 1995CrossRefGoogle Scholar
  22. 22.
    Herndon DN, Nguyen TT, Wolfe RR, Maggi SP, Biolo G, Muller M, Barrow RE: Lipolysis in burned patients Is stimulated by the β2-receptor for catecholamines. Arch Surg 129: 1301–1305, 1994CrossRefPubMedGoogle Scholar
  23. 23.
    Barbe P, Millet L, Galitzky J, Lafontan M, Berlan M: In situ assessment of the role of the β1-, β2-and β3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue. Br J Pharmacol 117: 907–913, 1996CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Granneman JG: Effects of agonist exposure on the coupling of β1 and β3 adrenergic receptors to adenylyl cyclase in isolated adipocytes. J Pharmacol Exp Ther 261: 638–642, 1992PubMedGoogle Scholar
  25. 25.
    Rosenbaum M, Malbon CC, Hirsch J, Leibel RL: Lack of β3-adrenergic effect on lipolysis in human subcutaneous adipose tissue. J Clin Endocrinol Metab 77: 352–355, 1993PubMedGoogle Scholar
  26. 26.
    Carpene C, Ambid L, Lafontan M: Predominance of β3-adrenergic component in catecholamine activation of lipolysis in garden dormouse adipocytes. Am J Physiol 266: R896–R904, 1994PubMedGoogle Scholar
  27. 27.
    Arner P: Adrenergic receptor function in fat cells. Am J Clin Nutr 55: 228S–236S, 1996Google Scholar
  28. 28.
    Langin D, Tavernier G, Lafontan M: Regulation of β3-adrenoceptor expression in white fat cells. Fund Clin Pharmacol 9: 97–106, 1995CrossRefGoogle Scholar
  29. 29.
    Arch JRS, Wilson S: β3-adrenoceptors and the regulation of metabolism in adipose tissues. Biochem Soc Transact 24: 412–418, 1996CrossRefGoogle Scholar
  30. 30.
    Ardévol A, Cañas X, Remesar X, Alemany M: Cooling rates of tissue samples during freezing with liquid nitrogen. J Biochem Biophys Meth 27: 77–86, 1993CrossRefPubMedGoogle Scholar
  31. 31.
    Tebar E, Ramirez I, Soley M: Epidermal growth factor modulates the lipolytic action of catecholamine in rat adipocytes. J Biol Chem 268: 17199–17204, 1993PubMedGoogle Scholar
  32. 32.
    Seguchi H, Nishimura J, Zhou Y, Niro N, Kumazawa J, Kanaide H: Expression of β3-adrenoceptors in rat detrusor smooth muscle. J Urol 159: 2197–2201, 1998CrossRefPubMedGoogle Scholar
  33. 33.
    Machida CA, Bunzow JR, Searles RP, van Tol H, Tester B, Neve KA, Teal P, Nipper V, Civelli O: Molecular cloning and expression of the rat β1-adrenergic receptor gene. J Biol Chem 265: 12960–12965, 1990PubMedGoogle Scholar
  34. 34.
    Gocayne J, Robinson DA, Fitzgerald MG, Chung F, Kerlavage AR, Lentes K, Lai J, Wang C, Fraser CM, Venter JC: Primary structure of rat cardiac β-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: Further evidence for a multigene family. Biochemistry 84: 8296–8300, 1987Google Scholar
  35. 35.
    Granneman JG, Lahners KN, Chaudhry A: Molecular cloning and expression of the rat β3-adrenergic receptor. Mol Pharmacol 40: 895–899, 1991PubMedGoogle Scholar
  36. 36.
    Danielson PE, Forss-Peter S, Brow MA, Calavetta L, Douglass J, Milner RJ, Sutcliffe JG: p1B15: A cDNA clone of the rat mRNA encoding cyclophilin. DNA 7: 261–267, 1988CrossRefPubMedGoogle Scholar
  37. 37.
    Zhao J, Unelius L, Bengtsson T, Cannon B, Nedergaard J: Coexisting β-adrenoceptor subtypes - significance for thermogenic process in brown fat cells. Am J Physiol 36: C969–C979, 1994Google Scholar
  38. 38.
    Krief S, Lönnqvist F, Raimbault S, Baude B, Van Spronsen A, Arner P, Strosberg AD, Ricquier D, Emorine LJ: Tissue distribution of β3-adrenergic receptor mRNA in man. J Clin Invest 91: 344–349, 1993CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Bégin-Heick N: β3-adrenergic activation of adenylyl cyclase in mouse white adipocytes: Modulation by GTP and effect of obesity. J Cell Biochem 58: 464–473, 1995CrossRefPubMedGoogle Scholar
  40. 40.
    Hausdorff WP, Caron MG, Lefkowitz RJ: Turning off the signal: Desensitization of β-adrenergic receptor function. FASEB J 4: 2881–2889, 1990PubMedGoogle Scholar
  41. 41.
    Vatner DE, Vatner SE, Nejima J, Uemura N, Susanni EE, Hintze TH, Homcy CJ: Chronic norepinephrine elicits desensitization by uncoupling the β-receptor. J Clin Invest 84: 1741–1748, 1989CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    van Liefde I, van Witzenburg A, Vauquelin G: Multiple β adrenergic receptor subclasses mediate the I-isoproterenol-induced lipolytic response in rat adipocytes. J Pharmacol Exp Ther 262: 552–558, 1992PubMedGoogle Scholar
  43. 43.
    Hollenga C, Zaagsma J: Direct evidence for the atypical nature of functional β-adrenoceptors in rat adipocytes. Br J Pharmacol 98: 1420–1424, 1989CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Cristina Cabot
    • 1
  • Maria del Mar Grasa
    • 1
  • José Antonio Fernández‐López
    • 1
  • Marià Alemany
    • 1
  1. 1.Centre Especial de Recerca en Nutrició i Ciència dels Aliments, Facultat de BiologiaUniversitat de BarcelonaBarcelonaSpain

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