Methods Used to Study the Involvement of Adenosine in the Regulation of Lipolysis

  • Bertil B. Fredholm


The evidence that adenosine plays a role in the regulation of adipose tissue circulation and metabolism is impressive. Adipose tissue offers many special advantages when studying intraarterial adenosine effects. It is possible to study relevant phenomena in preparations ranging from cell free systems, via isolated purified cells and intact pieces of white adipose tissue in vitro, to intact tissue perfused in situ. Furthermore, the biochemical steps mediating receptor effects are particularly well delineated in this tissue. The present chapter will, however, neither describe the evidence that adenosine is physiologically important in adipose tissue nor review the evidence regarding the biochemical regulation of lipolysis, but will instead focus on the techniques that may be and have been used in studying the role of adenosine in the regulation of adipose tissue function.


Adipose Tissue Adenylate Cyclase Adenosine Deaminase Adenosine Level Endogenous Adenosine 
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  1. Aktories, K., Schultz, G., and Jakobs, K. H. 1981. Na+ amplifies adenosine receptor-mediated inhibition of adipocyte adenylate cyclase. Europ. J. Pharmacol., 71: 157–160.CrossRefGoogle Scholar
  2. Aktories, K., Schultz, G., and Jakobs, K. H. 1981b. Adenosine receptor-mediated stimulation of GTP hydrolysis in adipocyte membranes. Life Sci., 30: 269–215.CrossRefGoogle Scholar
  3. Allen, D. O., Largis, E. E., Katocs, A. S., Jr., and Ashmore, J. 1975. Perifused fat cells. Methods Enzymol. 35: 607–612.PubMedCrossRefGoogle Scholar
  4. Belfrage, E., Hjemdahl, P., and Fredholm, B. B. 1979. Metabolic effects of blood flow restriction in adipose tissue. Acta Physiol. Scand., 105: 222–221.Google Scholar
  5. Brown, B. L., Eakins, R. P., and Albano, J. D. M. 1972. Saturation assay for cyclic AMP using endogenous binding protein, Adv. Cyclic Nucleotide Res., 2: 25-40.Google Scholar
  6. Ebert, R., and Schwabe, U. 1973. Studies on the antilipolytic effect of adenosine and related com-pounds in isolated fat cells. Naunyn Schmiedebergs Arch. Pharmacol., 278: 241–259.CrossRefGoogle Scholar
  7. Fain, J. N. 1975. Isolation of free brown and white fat cells. Methods Enzymol. 55: 555–561.CrossRefGoogle Scholar
  8. Fain, J. N. 1979. Effect of lipolytic agents on adenosine and AMP formation by fat cells. Biochim. Biophys. Acta, 575: 510–520.Google Scholar
  9. Fain, J. N., Pointer, R. H., and Ward, W. F. 1972. Effects of adenosine nucleosides on adenylate cyclase, phosphodiesterase, cyclic adenosine monophosphate accumulation, and lipolysis in fat cells. J. Biol. Chem., 247: 6866–6872.PubMedGoogle Scholar
  10. Fain, J. N., Shepherd, R. E., Malbon, C. C., and Moreno, F. J. 1978. Hormonal regulation of tri-glyceride breakdown in adipocytes. In: Disturbance in Lipid and Lipoprotein Metabolism, American Physiological Society pp. 213–228. Ed. by Dietschy, J. M., Gotto, A. M., and Ontko, J. A. Williams & Wilkins, Baltimore.Google Scholar
  11. Fredholm, B. B. 1970. Studies on the sympathetic regulation of circulation and metabolism in isolated canine subcutaneous adipose tissue, Acta Physiol. Scand. ( Suppl. ), 354: 1–41.Google Scholar
  12. Fredholm, B. B. 1971. The effect of lactate in canine subcutaneous adipose tissue in situ. Acta Physiol. Scand., 57: 110–123.CrossRefGoogle Scholar
  13. Fredholm, B. B. 1976. Release of adenosine-like material from isolated perfused dog adipose tissue following sympathetic nerve stimulation and its inhibition by adrenergic a-receptor blockade. Acta Physiol. Scand., 96: 422–430.Google Scholar
  14. Fredholm, B. B. 1978a. Local regulation of lipolysis by fatty acids, prostaglandins and adenosine. Med. Biol., 56: 249–261.PubMedGoogle Scholar
  15. Fredholm, B. B. 1978b. Effect of adenosine, adenosine analogues and drugs inhibiting adenosine inactivation on lipolysis in rat fat cells. Acta Physiol. Scand., 102: 191–198.Google Scholar
  16. Fredholm, B. B. 1984. Nervous control of circulation and metabolism in white adipose tissue. In: New Perspective in Adipose Tissue Structure, Function and Development, pp. 45–64. Ed. by Van, R. L. R., and Cryer, A. Butterworths, London.Google Scholar
  17. Fredholm, B. B., and Hjemdahl, P. 1976. Inhibition by acidosis of adenosine 3’, 5’-cyclic monophos-phate accumulation and lipolysis in isolated rat fat cells. Acta Physiol. Scand., 96: 160–169.Google Scholar
  18. Fredholm, B. B., and Hjemdahl, P. 1979. Uptake and release of adenosine in isolated rat fat cells. Acta Physiol. Scand., 105: 251–261.CrossRefGoogle Scholar
  19. Fredholm, B. B., and Lindgren, E. 1983. The effect of alkylxanthines and other phosphodiesterase inhibitors on adenosine-receptor mediated decrease in lipolysis and cyclic AMP accumulation in rat fat cells. Acta Pharmacol. Toxicol., 54: 64–11.Google Scholar
  20. Fredholm, B. B., and Rosell, S. 1968. Effect of adrenergic blocking agents on lipid mobilization from canine subcutaneous adipose tissue after sympathetic nerve stimulation. J. Pharmacol. Exp. Ther., 159: 1–1.PubMedGoogle Scholar
  21. Fredholm, B. B., and Rosell, S. 1970. Effects of prostaglandin Ei in canine subcutaneous adipose tissue in situ. Acta Physiol. Scand., 80: 450–458.Google Scholar
  22. Fredholm, B. B., and Sollevi, A. 1981. The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline. J. Physiol., 313: 351–367.PubMedGoogle Scholar
  23. Fredholm, B. B., Jonzon, B., Lindgren, E., and Lindstrom, K. 1982. Adenosine receptors mediating cyclic AMP production in the rat hippocampus. J. Neurochem., 39: 165–175.PubMedCrossRefGoogle Scholar
  24. Fredholm, B. B., Linde, B., and Persson, B. 1973. Effects of fasting on adipose tissue perfused in situ in young dogs. Scand. J. Clin. Lab. Invest., 57: 79–86.Google Scholar
  25. Fredholm, B. B., Linde, B., Prewitt, R., Jr., and Johnson, P. C. 1976. Oxygen uptake and tissue oxygen tension in canine subcutaneous adipose tissue during adrenergic stimulation. Acta Physiol. Scand., 97: 48–59.PubMedCrossRefGoogle Scholar
  26. Fredholm, B. B., Oberg, B., and Rosell, S. 1970. Effect of vasoactive drugs on circulation in canine subcutaneous adipose tissue. Acta Physiol. Scand., 79: 564–574.Google Scholar
  27. Gammeltoft, S., Glieman, J., Vinter, J., and Osterlind, K. 1972. A technique for rapid separation of isolated fat cells from their incubation medium. Acta Physiol. Scand., 84: 16–32.Google Scholar
  28. Green, A., and Newsholme, E. A. 1981. Distribution of adenosine metabolizing enzymes between adipocyte and stroma-vascular cells of adipose tissue. Biochim. Biophys. Acta, 676: 122–124.PubMedCrossRefGoogle Scholar
  29. Hedqvist, P., and Fredholm, B. B. 1976. Effects of adenosine on adrenergic neurotransmission: prejunctional inhibition and postjunctional enhancement. Nannyn Schmiedebergs Arch. Pharmacol., 295: 217–223.Google Scholar
  30. Hjemdahl, P., and Fredholm, B. B. 1976a. Cyclic AMP-dependent and independent inhibition of lipolysis by adenosine and decreased pH. Acta Physiol. Scand., 96: 170–179.Google Scholar
  31. Hjemdahl, P., and Fredholm, B. B. 1976b. Influence of adipose tissue blood flow on the lipolytic response to circulating noradrenaline of normal and reduced pH. Acta Physiol. Scand., 98: 14–79.Google Scholar
  32. Hjemdahl, P., and Sollevi, A. 1978. Antilipolytic effect of adenosine in isolated perfused fat cells. Acta Physiol. Scand., 705: 270–274.CrossRefGoogle Scholar
  33. Jarett, L. 1974. Subcellular fractionation of adipocytes. In: Methods in Enzymology, Volume 31, pp. 60–71. Ed. by Fleischer, S., and Parker, L., Academic Press, New York.Google Scholar
  34. Laurell, S., and Tibbling, G. 1966. An enzymatic fluorimetric micromethod for the determination of glycerol. Clin. Chim. Acta, 75: 317–322.Google Scholar
  35. Linde, B. 1976. Studies on the vascular exchange function in canine subcutaneous adipose tissue. Acta Physiol. Scand. ( Suppl. ), 433: 1–43.Google Scholar
  36. Linde, B., Chisholm, G., and Rosell, S. 1974. The influence of sympathetic activity and histamine on the blood-tissue exchange of solutes in canine adipose tissue. Acta Physiol. Scand., 92: 154–155.CrossRefGoogle Scholar
  37. Londos, C., Wolff, J., and Cooper, D. M. F. 1979. Action of adenosine on adenylate cyclase. In: Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides, pp. 271–281 Ed. by Baer H. P., and Drummond, G. I. Raven Press, New York,Google Scholar
  38. Nedergaard, J., and Lindberg, O. 1982. The brown fat cell. Int. Rev. Cytol., 187–286.Google Scholar
  39. Nilsson, N. O. 1981. Studies on the short term regulation of lipolysis in rat fat cells with special regard to the anti-lipolytic effect of insulin. Doctoral Thesis for the Department of Biochemistry, Lund, pp. 1–43.Google Scholar
  40. Nilsson, N. O., and Belfrage, P. 1981. Continuous measurement of free fatty acid release from intact adipocytes by pH-stat titration. Methods Enzymol. 72: 319–325.PubMedCrossRefGoogle Scholar
  41. Oberg, B., and Rosell, S. 1967. Sympathetic control of consecutive vascular sections in canine subcutaneous adipose tissue. Acta Physiol. Scand., 77: 47–56.CrossRefGoogle Scholar
  42. Oro, L., Rosell, S., and Wallenberg, L. 1965. Circulatory and metabolic processes in adipose tissue in vivo. Nature, 205: 178–179.PubMedCrossRefGoogle Scholar
  43. Rodbell, M. 1964. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J. Biol. Chem., 259: 375–380.Google Scholar
  44. Rosell, S. 1966. Release of free fatty acids from subcutaneous adipose tissue in dogs following sympathetic nerve stimulation. Acta Physiol. Scand., 67: 343–351.Google Scholar
  45. Rosenblit, P. D., and Levy, D. 1980. Photoaffinity labelling of the adenosine transport system in adipocyte plasma membranes. Arch. Biochem. Biophys., 204: 331–339.PubMedCrossRefGoogle Scholar
  46. Schonhofer, P. S., and Skidmore, I. F. 1971. Studies on the conditions for cyclic AMP formation in homogenized and intact fat cells by use of 3H-ATP and 3H-adenine. Pharmacology, 6: 109–125.PubMedCrossRefGoogle Scholar
  47. Schwabe, U., Ebert, R., and Erbler, H. C. 1973. Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3’, 5’-AMP levels and lipolysis. Naunyn Schmiedebergs Arch. Pharmacol., 275: 133–148.CrossRefGoogle Scholar
  48. Sollevi, A., and Fredholm, B. B. 1981a. Role of adenosine in adipose tissue circulation. Acta Physiol. Scand., 772: 293–298.CrossRefGoogle Scholar
  49. Sollevi, A., and Fredholm, B. B. 1981b. The antilipolytic effect of endogenous and exogenous adenosine in canine adipose tissue in situ. Acta Physiol. Scand., 113: 53–60.PubMedCrossRefGoogle Scholar
  50. Sollevi, A., and Fredholm, B. B. 1983. Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue. Acta Physiol. Scand., 119: 15–24.PubMedCrossRefGoogle Scholar
  51. Sollevi, A., Hjemdahl, P., and Fredholm, B. B. 1981. Endogenous adenosine inhibits lipolysis induced by nerve stimulation without inhibiting noradrenaline release in canine subcutaneous adipose tissue in vivo, Naunyn Schmiedebergs Arch. Pharmacol., 316: 112–119.Google Scholar
  52. Solomon, S. S., Turpin, B. P., and Duckworth, W. C. 1980. Comparative studies of the antilipolytic effect of insulin and adenosine in the perifused isolated cell. Horm. Metab. Res., 72: 601–604.CrossRefGoogle Scholar
  53. Steinberg, D., Mayer, S. E., Khoo, J. C., Miller, E. A., Miller, R. E., Fredholm, B. B., and Eichner, R. 1975. Hormonal regulation of lipase, phosphorylase and glycogen synthase in adipose tissue. Adv. Cyclic Nucleotide Res., 5: 549–568.PubMedGoogle Scholar
  54. Stralfors, P., and Belfrage, P. 1984. Reversible phosphorylation of hormone-sensitive lipase/cholesterol ester hydrolase in the hormonal control of adipose tissue lipolysis and of adrenal stereoidogenesis. In: Molecular Aspects of Cellular Regulation. Recently Discovered Systems of Enzyme Regulation by Reversible Phosphorylation—Further Advances, pp. 27–62. Ed. by Cohen, P., ElSciver, Am-sterdam. In press.Google Scholar
  55. Trost, T., and Schwabe, U. 1981. Adenosine receptors in fat cells. Identification by (-)-N6-[3H]-phen- ylisopropyladenosine binding. Mol. Pharmacol., 19: 228–235.Google Scholar
  56. Trost, T., and Stock, K. 1977. Effects of adenosine derivatives on cAMP accumulation and lipolysis in rat adipocytes and on adenylate cyclase in adipocyte plasma membranes. Naunyn Schmie- deberg’s Arch. Pharmacol., 299: 33–40.CrossRefGoogle Scholar
  57. Turpin, B. P., Duckworth, W. C., and Solomon, S. S. 1977. Perifusion of isolated rat adipose cells. Modulation of lipolysis by adenosine. J. Clin. Invest., 60: 442–448.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Bertil B. Fredholm
    • 1
  1. 1.Department of PharmacologyKarolinska InstituteStockholmSweden

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