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Effects on energy utilization of a ß3-adrenergic agonist in rats fed on a cafeteria diet

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Abstract

The antiobesity potential of a new ß3-adrenergic agonist (Trecadrine) was assessed in a cafeteria model of obesity through body composition, thermogenesis and oxygen consumption indicators. Animals fed on a cafeteria diet for 75 days increased body weight and fat content, while muscle mass as a percentage of body weight was reduced in relation to control fed rats. In addition, in vitro brown adipose tissue (BAT) and white adi pose tissue (WAT) oxygen consumption was increased in these obese animals as compared with controls. Trecadrine administration reduced weight gain, BAT and WAT stores as wel as the respiratory quotient, which was accompanied by an increase in WAT and BAT oxygen consumption and rectal temperature. Moreover, muscle mass as a percentage of body weigh maintained the same values as non-obese animals, while an increase in absolute muscle weight was found in Trecadrine-treated obese rats. However, liver weights and in vitro oxygen consumption remained unaltered after cafeteria feeding and Trecadrine administration Since chronic administration of Trecadrine had no effect on food intake, the stimulation o thermogenesis and oxygen consumption by the ß3-adrenergic agonist in white and brown adipose tissue are apparently responsible for the rise in energy expenditure as well as for the lower weight gain and fat deposition in obese treated rats. Thus, Trecadrine exhibits some promise as a potential treatment for obesity.

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References

  1. Ravussin E., Swinburn B.A.: Energy expenditure and obesity. Diab. Rev., 4, 403–422, 1996.

    Google Scholar 

  2. Bray G.A.: Pathophysiology of obesity. Am. J. Clin. Nutr., 55, 488–494, 1992.

    Google Scholar 

  3. Stunkard A.J.: Current views on obesity. Am. J. Med., 100, 230–236, 1995.

    Article  Google Scholar 

  4. Ferrannini E.: Obesity. The case for medical intervention. Metabolism, 44, 1–27, 1995.

    Article  Google Scholar 

  5. Seidell J.C.: The impact of obesity on health status: some implications for health care costs. Int. J. Obes., 19, S13–S16, 1995.

    Google Scholar 

  6. Bray G.A.: Pharmacologic treatment of obesity: Symposium Overview. Obesity Research, 3, 415–417, 1995.

    Article  Google Scholar 

  7. Rossner S.: Long-term intervention strategies in obesity treatment. Int. J. Obes., 19, S29–S33, 1995.

    Google Scholar 

  8. Arch J.R.S., Wilson S.: Prospects for ß3-adrenoceptor agonists in the treatment of obesity and diabetes. Int. J. Obes., 20, 191–199, 1996.

    CAS  Google Scholar 

  9. Yen T.T.: ß-agonists as antiobesity, antidiabetic and nutrient partitioning agents. Obesity Research, 3 (suppl. 4), 531–536, 1995.

    Article  Google Scholar 

  10. Goldberg D.E., Prentice A.M., Murgatroyd P.R., Haines W., Tuersley M.D.: Effects on metabolite rate and fuel selection of a selective ß-3 agonist (ICI D7114) in healthy lean men. Int. J. Obes., 19, 625–631, 1995.

    CAS  Google Scholar 

  11. Himms-Hagen J., Cui J., Danforth E. Jnr., Taatjes D.J., Lang S.S., Waters B.L., Claus T.H.: Effect of Cl-316,243, a thermogenic ß3-agonist, on energy balance and brown and white adipose tissues in rats. Am. J. Physiol., 266, 1371–1382, 1994.

    Google Scholar 

  12. Yoshida T., Sakane N., Wakabayashi Y., Umekawa T., Kondo M.: Anti-obesity and anti-diabetic effects of Cl 316,243, a highly specific ß3-adrenoceptor agonist in yellow KK mice. Life Sci., 54, 491–498, 1994.

    Article  CAS  PubMed  Google Scholar 

  13. Carroll M.J., Lister C.A., Sennitt M.V., Stewart-Long N., Cawthorne M.A.: Improved glycemic control in C57BL/KsJ (db/db) mice after treatment with the termogenic ß-adrenoceptor agonist BRL 26830. Diabetes, 34, 1198–1203, 1985.

    Article  CAS  PubMed  Google Scholar 

  14. Chapman B.J., Farquahar D.L., Galloway S.M., Simpson G.K., Munro J.K.: The effects of a new ß-adrenoreceptor agonist BRL 26830A in refractory obesity. Int. J. Obes., 12, 119–123, 1988.

    CAS  PubMed  Google Scholar 

  15. Wilson S., Thurlby P.L., Arch J.R.S.: Substrate supply for thermogenesis induced by the ß-adrenoceptor agonist BRL 26830A. Can. J. Physiol. Pharmacol., 65, 113–119, 1987.

    Article  CAS  PubMed  Google Scholar 

  16. Yoshida T., Hiraoka N., Yoshioka K.: Antiobesity and antidiabetic actions of a ß3-adrenoceptor agonist, BRL 26830A, in yellow KK mice. Endrocrinol. Jpn., 38, 397–403, 1991.

    CAS  Google Scholar 

  17. Meier Mk., Alig L., Burgi-Saville M.E., Muller M.: Phenethanolamine derivatives with calorigenic and antidiabetic qualities. Int. J. Obes., 8 (suppl.1), 215–225, 1984.

    CAS  PubMed  Google Scholar 

  18. Yen T.T., McKee M.M., Stamm N.B.: Thermogenesis and weight control. Int. J. Obes., 8 (suppl. 1), 65–78, 1984.

    CAS  PubMed  Google Scholar 

  19. Bloom J.D., Dutin M.D., Johnson B.D., Wissner A., Burns M.G., Largis E.E., Dolan J.A., Claus T.H.: Disodium (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243). A potent ß-adrenergic agonist virtually specific for ß3 receptors. A promising antidiabetic and antiobesity agent. J. Med. Chem., 35, 3081–3084, 1992.

    Article  CAS  PubMed  Google Scholar 

  20. Holloway B.R., Howe R., Rao B.S., Stribling D.: ICI D7114 a novel selective ß-adrenoreceptor agonist selectively stimulates brown fat and increases whole body oxygen consumption. Br. J. Pharmacol., 104, 97–104, 1991.

    Article  CAS  PubMed  Google Scholar 

  21. Holloway B.R., Howe R., Rao B.S., Stribling D.: ICI D7114: a novel selective adrenoreceptor agonist of brown fat and thermogenesis. Am. J. Clin. Nutr., 55, 262–264, 1992.

    Google Scholar 

  22. Belay T., Guy T.A.: ß1- and ß2-adrenoceptor antagonist activities of ICI-215001, a putative ß3-adrenoceptor agonist. Br. J. Pharmacol., 112, 55–58, 1994.

    Article  Google Scholar 

  23. Holloway B.R.: Selective ß-agonists of brown fat and thermogenesis. In: Lardy H., Stritman F. (Eds.) Hormones, Thermogenesis, and Obesity. New York, Elsevier, 1989, pp. 477–484.

    Google Scholar 

  24. Yen T.T.: The antiobesity and metabolic activities of LY79771 in obese and normal mice. Int. J. Obes., 8, 69–78, 1984.

    CAS  PubMed  Google Scholar 

  25. Meier M.K., Blum-Kaelin D., Gerold M., Isler D., Mueller M.: Ro 40-2148, a novel thermogenic ß-agonist with anti-obesity activity. In: Bjorntorp P., Rossner S. (Eds.) Obesity in Europe. London, John Libbey, 1989, pp. 329–338.

    Google Scholar 

  26. Cawthorne M.A., Sennitt M.V., Arch J.R.S., Smith S.A.: BRL 35135, a potent and selective atypical ß-adrenoceptor agonist. Am. J. Clin. Nutr., 55, 252–257, 1992.

    Google Scholar 

  27. Charon C., Dupoy F., Marie V., Bazin R.: Effect of the ß-adrenoceptor agonist BRL-35135 on development of obesity in suckling Zucker (fa/fa) rats. Am. J. Physiol., 268, 1039–1045, 1995.

    Google Scholar 

  28. Hashimoto K., Hagao Y., Ida K.: Improvement of metabolic disorders and visceral fat obesity by the ß3-adrenoceptor agonist (R*,R*)-(±)-Methyl-4-[2-[2-hydroxy-2-3-chlorophenyl) ethylamino] propyl]-phenoxyacetate hydrobromide (BRL 35135A) in genetically obese rodents. Biochem. Pharmacol., 52, 1529–1535, 1996.

    Article  CAS  PubMed  Google Scholar 

  29. Santti E., Huupponen R., Rouru J., Hänninen V., Pesonen U., Jhanwar-Uniyal M., Koulu M.: Potentiation of the anti-obesity effect of the selective ß3-adrenoceptor agonist BRL 35135 in obese Zucker rats by exercise. Br. J. Pharmacol., 113, 1231–1236, 1994.

    Article  CAS  PubMed  Google Scholar 

  30. Galitzky J., Carpane C., Lafontan M., Berlan M.: Stimulation spécifique des récepteurs ß3-adrénergiques du tissu adipeux par l’octopamine. Life Sci., 316, 519–523, 1993.

    CAS  Google Scholar 

  31. Strosberg A.D., Pietri-Rouxel F.: Function and regulation of the ß3-adrenoceptor. Trends Pharmacol. Sci., 17, 373–381, 1996.

    Article  CAS  PubMed  Google Scholar 

  32. Barrionuevo M., Milagro F.I., Cenazurrabeitia E., Martinez J.A.: Potential anti-diabetic applications of a new molecule with affinity for ß3-adrenoceptors. Life Sci., 59, 141–146, 1996.

    Article  Google Scholar 

  33. Diez-Sampedro A., Milagro F.I., Berraondo B., Zulet M.A., Martinez J.A., Barber A.: Effects of Trecadrine, a ß3-adrenergic agonist, on intestinal absorption of D-galactose and disaccharidase activities in three physiopathological models. J. Pharm. Pharmacol., 49, 873–877, 1997.

    Article  CAS  PubMed  Google Scholar 

  34. Martinez A., Berraondo B., Perez R., Frühbeck G., Fernandez-Otero M.P.: Slimming effect and lipolitic activity of a new molecule with affinity for ß3-adrenergic receptors. Faseb J., 10, 504A, 1996.

    Google Scholar 

  35. Rothwell N.J., Stock M.J.: Energy balance and mitrochondrial function in liver and brown fat of rats fed “cafeteria” diets of varying protein content. J. Nutr., 112, 1663–1672, 1982.

    CAS  PubMed  Google Scholar 

  36. Morbach A.C., Brans Y.W.: Determination of body composition in growing rats by total body electrical conductivity. J. Pediatr. Gastroenterol. Nutr., 14, 283–292, 1992.

    Article  CAS  PubMed  Google Scholar 

  37. Martinez J.A., García-Granero M., Frühbeck G.: Role of fragment peptides from ob protein on body weight and thermogenesis control: a screening. J. Physiol. Biochem., 52, 123–124, 1996.

    CAS  Google Scholar 

  38. Berraondo B., Milagro F., Perez R., Zulet M.A., Martinez J.A.: Lipid and carbohydrate utilization in a dietary model of obesity. Proc. Nutr. Soc., 54, 156A, 1995.

    Google Scholar 

  39. Astrup A., Toubro S., Christensen N.J., Quaade F.: Pharmacology of thermogenic drugs. Am. J. Clin. Nutr., 55, 246–248, 1992.

    Google Scholar 

  40. Arch J.R.S., Ainsworth A.T., Cawthorne M.A., et al.: Atypical ß-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature, 309, 163–165, 1984.

    Article  CAS  PubMed  Google Scholar 

  41. Hollenga C., Zaagsma J.: Direct evidence for the atypical nature of functional ß-adrenoceptors in rat adipocytes. Br. J. Pharmacol., 98, 1420–1424, 1989.

    Article  CAS  PubMed  Google Scholar 

  42. Emorine L.J., Marullo S., Briend-Sutren M., Patey G., Tate T., Delavier-Klutchko C., Strosberg A.D.: Molecular characterization of the human ß3-adrenergic receptor. Science, 245, 1118–1121, 1989.

    Article  CAS  PubMed  Google Scholar 

  43. Granneman J.G., Lahners K.N., Chaudhry A.: Molecular cloning and expression of the rat ß3-adrenergic receptor. Mol. Pharmacol., 40, 895–899, 1991.

    CAS  PubMed  Google Scholar 

  44. Muzzin P., Revelli J.P., Kuhne F., Gocayne J.D., McCombie W.R., Venter J.C., Giacobino J., Fraser C.M.: An adipose tissue specific ß-adrenergic receptor. Molecular cloning and downregulation in obesity. J. Biol. Chem., 266, 24053–24058, 1991.

    CAS  PubMed  Google Scholar 

  45. Nahmias C., Blin N., Elalouf J.M., Mattei M.G., Strosberg A.D., Emorine L.J.: Molecular characterization of the mouse ß3-adrenergic receptor: Relationship with the atypical receptor of adipocytes. EMBO J., 10, 3721–3727, 1991.

    CAS  PubMed  Google Scholar 

  46. Yen T.T.: Antiobesity and antidiabetic ß-agonists: lessons learned and questions to be answered. Obes. Res., 2, 472–480, 1994.

    Article  CAS  PubMed  Google Scholar 

  47. Yen T.T.: ß-adrenergic agonists as nutrient repartitioning agents. In: Bray G.A., Ryan D.H., (Eds.) Pennington Center Nutrition Series, Vol 2, The Science of Food Regulation: Food Intake, Taste, Nutrient Partitioning, and Energy Expenditure. Baton Rouge, Louisiana State University Press, 1992, pp. 150–163.

    Google Scholar 

  48. Rolls B.J., Rowe E.D., Turner R.C.: Persistent obesity in rats following a period of consumption of a mixed, high energy diet. J. Physiol., 298, 415–427, 1980.

    CAS  PubMed  Google Scholar 

  49. Schepper J.D., Zhou Z., Louis O., Velkeniers B., Hooghe-Peters E., Vanhaelst L.: The weight gain and ultimate adiposity in cafeteria diet. Induced obesity is unrelated to the central serotoninergic tonus. Eating Weight Disord., 1, 38–43, 1997.

    Article  Google Scholar 

  50. Almond R.E., Cawthorne M.A., Enser M.: Muscles of diabetic db/db mice: fibre size, fibre-type and the effects of a thermogenic, ß-adrenoceptor agonist. Int. J. Obes., 12, 81–91, 1988.

    CAS  PubMed  Google Scholar 

  51. Martinez J.A., Rodriguez-Mariscal M., Del Barrio A.S., Larralde J.: Changes in serum and urinary amino acids after the administration of a mixed beta-adrenergic agonist. Ann. Nutr. Metab., 36, 328–335, 1992.

    Article  CAS  PubMed  Google Scholar 

  52. Portillo M.P., Del Barrio A.S., Garcia-Calonge M.A., Martinez J.A.: Desensitization effect of in vivo treatment with metaproterenol on beta1, beta2, and beta3-adrenergic responsiveness in rat adipocytes. Life Sci., 58, 405–414, 1996.

    Article  CAS  PubMed  Google Scholar 

  53. Lafontan M., Berlan M.: Fat cell α2-adrenoceptors: the regulation of fat cell function and lipolysis. Endrocrinol. Rev., 16, 716–738, 1995.

    CAS  Google Scholar 

  54. Barber P., Stich., Galitzky J., Kunesova M., Lafontan M., Berlan M.: In vivo increase in beta adrenergic lipolytic response in subcutaneous adipose tissue of obese subjects submitted to a hypocaloric diet. J. Clin. Endocrinol. Metab., 82, 63–69, 1997.

    Google Scholar 

  55. Sipiläinen R., Uusitupa M., Heikkinen S., Rissanen A., Laakso M.: Polymorphism of the ß3-adrenergic receptor gene affects basal metabolic rate in obese Finns. Diabetes, 46, 77–80, 1997.

    Article  PubMed  Google Scholar 

  56. Fleury C., Neverova M., Collins S., Raimbault S., Champigny O., Levi-Meyrueis C., Bouillaud F., Seldin M.F., Surwitt R.S., Ricquier D., Warden C.H.: Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia, Nature Genetics, 15, 269–272, 1997.

    Article  CAS  PubMed  Google Scholar 

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Berraondo, B., Bonafonte, A., Fernandez-Otero, M.P. et al. Effects on energy utilization of a ß3-adrenergic agonist in rats fed on a cafeteria diet. Eat Weight Disord 2, 130–137 (1997). https://doi.org/10.1007/BF03339963

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