Hormonal Regulation of Lipolysis: Role of Cyclic Nucleotides, Adenosine, and Free Fatty Acids

  • J. N. Fain
  • R. E. Shepherd
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 111)


Twenty years ago, Dole (1956) and Gordon and Cherkes (1956) presented evidence that lipid is mobilized from adipose tissue in the form of free fatty acids noncovalently bound to plasma albumin. The fatty acids are taken up by muscle, liver, and other tissues where they are either oxidized as a source of energy or reesterified. In addition, free fatty acids (FFA) may also be converted to ketone bodies by liver and, subsequently, oxidized by muscle and the brain as a source of energy.


Free Fatty Acid Adenylate Cyclase Hormonal Regulation Adenosine Deaminase Triglyceride Lipase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Angel, A., Desai, K.S., and Halperin, M.L. (1971). Reduction in adipocyte ATP by lipolytic agents: Relation to intracellular free fatty acid accumulation. J. Lipid Res. 12: 203 - 211.PubMedGoogle Scholar
  2. Birnbaumer, L. and Rodbell, M. (1969). Adenyl cyclase in fat cells. II. Hormone receptors. J. Biol. Chem. 244: 3477 - 3482.PubMedGoogle Scholar
  3. Boyd, T.A., Weiser, P.B., and Fain, J.N. (1975). Lipolysis and cyclic AMP accumulation in isolated fat cells from chickens. Gen. Comp. Endocrinol. 26: 243 - 247.PubMedCrossRefGoogle Scholar
  4. Burns, T.W., Langley, P.E., and Robison, G.A. (1975). Site of free-fatty acid inhibition of lipolysis by human adipocytes. Metabolism 24: 265 - 276.PubMedCrossRefGoogle Scholar
  5. Butcher, R.W. and Baird, C.E. (1969). The regulation of cyclic AMP and lipolysis in adipose tissue by hormones and other agents. pp. 5 - 23. In W.L. Holmes, L.A. Carlson, aid R. Paoletti (Eds.) Drugs Affecting Lipid Metabolism. Plenum Press, New York.CrossRefGoogle Scholar
  6. Butcher, R.W., Sneyd, J.G.T., Park, C.R., and Sutherland, E.J. Jr. (1966). Effect of insulin on adenosine 3′5′-monophosphate in the rat epididymal fat pad. J. Biol. Chem. 241: 1651 - 1653.PubMedGoogle Scholar
  7. Chlouverakis, C. (1963). Parasympathomimetic agents and the me- tabolism of rat adipose tissue. Metabolism 12: 936 - 940.PubMedGoogle Scholar
  8. Corbin, J.D., Reimann, E.M., Walsh, D.A., and Krebs, E.G. (1969). A cyclic AMP-stimulated protein kinase in adipose tissue. Biochem. Biophys. Res. Commun. 36: 328 - 336.PubMedCrossRefGoogle Scholar
  9. Dalton, C. and Hope, H.R. (1973). Inability of prostaglandin synthesis inhibitors to affect adipose tissue lipolysis. Prostaglandins 4: 641 - 651.PubMedGoogle Scholar
  10. Dalton, C. and Hope, W.C. (1974). Cyclic AMP regulation of prostaglandin biosynthesis in fat cells. Prostaglandins 6: 227 - 242.PubMedGoogle Scholar
  11. Desai, K.S., Li, K.C., and Angel, A. (1973). Bimodal effect of insulin on hormone-stimulated lipolysis: Relation to intracellular 3′,5′-cyclic adenylic acid and free fatty acids levels. J. Lipid Res. 14: 674 - 655.Google Scholar
  12. Dole, V.P. (1956). A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J. Clin. Invest. 35: 150 - 154.PubMedCrossRefGoogle Scholar
  13. Fain, J.N. (1971). Effects of menadione and vitamin K5 on glucose metabolism. respiration, lipolysis, cyclic 3′5′-adenylic acid accumulaiton, and adenyl cyclase in white fat cells. Mo Z. Pharmacol. 7:465-479.Google Scholar
  14. Fain, J.N. (1973a). Biochemical aspects of drug and hormone action on adipose tissue. Pharmacol. Rev. 25: 67 - 118.PubMedGoogle Scholar
  15. Fain, J.N. (1973b). Inhibition of adenosine cyclic 3′5′-monophosphate accumulation in fat cells by adenosine, N6 (phenyl-isopropyl) adenosine, and related compounds. Mol. Pharmacol. 9: 595 - 604.PubMedGoogle Scholar
  16. Fain, J.N. (1975). Insulin as an activator of cyclic AMP accumu- lation in rat fat cells. J. Cyclic Nuc. Res. 1: 359 - 366.Google Scholar
  17. Fain, J.N. (1977). Cyclic nucleotides in adipose tissue. In H. Cramer and J. Schultz (Eds.) Cyclic Nucleotides: Mechanisms of Action. John Wiley, London.Google Scholar
  18. Fain, J.N. and Butcher, F.R. (1976). Cyclic guanosine 3′,5′-monophosphate and the regulation of lipolysis in rat fat cells. J. Cyclic Nuc. Res. 2: 71 - 78.Google Scholar
  19. Fain, J.N., Dodd, A., and Novak, L. (1971). Enzyme regulation in gluconeogenesis and lipogenesis: Relationship of protein synthesis and cyclic AMP to lipolytic growth hormone and glucocorticoids. Metabolism 20: 109 - 118.PubMedCrossRefGoogle Scholar
  20. Fain, J.N. and Loken, S.C. (1971). Valinomycin as an antilipolytic agent. Effects on cyclic 3′5′-adenylic acid, adenyl cyclase, respiration,and glucose metabolism in brown and white fat cells. Mol. Pharmacol. 7: 455 - 464.PubMedGoogle Scholar
  21. Fain, J.N., Pointer, R.H., and Ward, W.F. (1972). Effects of adenosine nucleotides on adenylate cyclase, phosphodiesterase, cyclic adenosine monophosphate accumulation, and lipolysis in fat cells. J. BioZ. Chem. 247: 6866 - 6872.Google Scholar
  22. Fain, J.N., Psychoyos, S., Czernik, A.J., Frost, S., and Cash, W.D. (1973). Indomethacin, lipolysis and cyclic AMP accumulation in white fat cells. Endocrinology 93: 632 - 639.PubMedCrossRefGoogle Scholar
  23. Fain, J.N. and Rosenberg, L. (1972). Antilipolytic action of insulin on fat cells. Diabetes 21: 414 - 425.PubMedGoogle Scholar
  24. Fain, J.N. and Saperstein, R. (1970). The involvement of RNA synthesis and cyclic AMP in the activation of fat cell lipolysis by growth hormone and glucocorticoids. pp. 20 - 27. In B. Jeanrenaud and D. Hepp (Eds.) Adipose Tissue: Regulation and Metabolic Functions. Academic Press, New York.Google Scholar
  25. Fain, J.N. and Shepherd, R.E. (1975). Free fatty acids as feedback regulators of adenylate cyclase and cyclic 3′5′-AMP accumulation in rat fat cells. J. BioZ. Chem. 250: 6586 - 6592.Google Scholar
  26. Fain, J.N. and Shepherd, R.E. (1976). Inhibition of adenosine 3′5′-monophosphate accumulation in white fat cells by short chain fatty acids, lactate and (3-hydroxybutyrate. J. Lipid Res. 17: 377 - 385.PubMedGoogle Scholar
  27. Fain, J.N. and Wieser, P.B. (1975). Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis and glucose metabolism of fat cells. J. Biol. Chem. 250: 1027 - 1034.PubMedGoogle Scholar
  28. Fredholm, B.B. and Hedquist, P. (1975). Indomethacin and the role of prostaglandins in adipose tissue. Biochem. Pharmacol. 24: 61 - 66.PubMedCrossRefGoogle Scholar
  29. Gordon, R.S. Jr. and Cherkes, A. (1956). Unesterified fatty acids in human blood plasma. J. Clin. Invest. 35: 206 - 212.PubMedCrossRefGoogle Scholar
  30. Gorman, R.R. (1975). Prostaglandin endoperoxides: Possible new regulators of cyclic nucleotide metabolism. J. Cyclic Nuc. Res. 1: 1 - 9.Google Scholar
  31. Gorman, R.R., Hamberg, M., and Samuelson, B. (1975). Inhibition of basal and hormone-stimulated adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide prostaglandin H2. J. Biol. Chem. 250: 6460 - 6463.PubMedGoogle Scholar
  32. Hamberg, M. and Samuelsson, B. (1974). Prostaglandin endoperoxides. Novel transformation of arachidonic acid in human platelets. Proc. Nat. Acad. Sci. U.S.A. 71: 3400 - 3404.CrossRefGoogle Scholar
  33. Haslam, R.J. and Rosson, G.M. (1975). Effects of adenosine on levels of adenosine cyclic 3′5′-monophosphate in human blood platelets in relation to adenosine incorporation and platelet aggregation. Mol. Pharm. 11: 528 - 544.Google Scholar
  34. Ho, R.J., Bomboy, J.D., Wasner, H.K., and Sutherland, E.W. (1975). Preparation and characterization of a hormone antagonist from adipocytes. Meth. in Enzymol. 39:431-438.Google Scholar
  35. Ho, R.J. and Sutherland, E.W. (1971). Formation and release of a hormone antagonist by rat adipocytes. J. Biol. Chem. 246: 6822 - 6827.PubMedGoogle Scholar
  36. Illiano, G. aid Cuatrecasas, P. (1971). Endogenous prostaalandins modulate lipolytic processes in adipose tissue. Nature New Biol. 234: 72 - 74PubMedGoogle Scholar
  37. Illiano, G., Tell, G.P.E., Siegel, M.I., and Cuatrecasas, P. (1973). Guanosine 3′,5′-cyclic monophosphate and the action of insulin. Proc. Nat. Acad. Sci. U.S.A. 70: 2443 - 2447.CrossRefGoogle Scholar
  38. Jungas, R.L. (1966). Role of cyclic-3′5′-AMP in the response of adipose tissue to insulin. Proc. Nat. Acad. Sci. U.S.A. 56: 757 - 763.CrossRefGoogle Scholar
  39. Khoo, J.C., Aguino, A.A., and Steinberg, D. (1974). The mechanism of activation of hormone-sensitive lipase in human adipose tissue. J. Clin. Invest. 53: 1124 - 1131.PubMedCrossRefGoogle Scholar
  40. Khoo, J.C. and Steinberg, D. (1974). Reversible protein kinase activation of hormone-sensitive lipase from chicken adipose tissue. J. Lipid Res. 15: 602 - 610.PubMedGoogle Scholar
  41. Khoo, J.C., Steinberg, D., Thompson, B., and Mayer, S.E. (1973). Hormonal regulation of adipocyte enzymes. J. Biol. Chem. 248: 3823 - 3830.PubMedGoogle Scholar
  42. Kitabgi, P., Rosselin, G., and Bataille, D. (1976). Interactions of glucagon and related peptides with chicken adipose tissue. Horm. Metab. Res. 8: 266 - 270.PubMedCrossRefGoogle Scholar
  43. Knight, B.L. and Iliffe, J. (1973). The effect of glucose, insulin and noradrenaline on lipolysis and on the concentrations of adenosine 3′5′-monophosphate and adenosine 5′-triphosphate in adipose tissue. Biochem. J. 132: 77 - 82.PubMedGoogle Scholar
  44. Kono, T. and Barham, F.W. (1973). Effects of insulin on the levels of adenosine 3′5′-monophosphate and lipolysis in isolated rat epididymal fat cells. J. Biol. Chem. 248: 7417 - 7426.PubMedGoogle Scholar
  45. Lamberts, S.W.J., Timmermans, H.A.T., Kramer-Blankestijn, M., and Birkenhager, J. (1975). The mechanism of the potentiating effect of glucocorticoids on catecholamine-induced lipolysis. Metabolism 24: 681 - 689.PubMedCrossRefGoogle Scholar
  46. Loten, E.G. and Sneyd, J.G.T. (1970). An effect of insulin on adipose-tissue adenosine 3′5-cyclic monophosphate phosphodiesterase. Biochem. J. 120: 187 - 193.PubMedGoogle Scholar
  47. Malgieri, J.A., Shepherd, R.E., and Fain, J.N. (1975). Lack of feedback regulation of cyclic 3′5′AMP accumulation by free fatty acids in chicken fat calls. J. Biol. Chem. 250: 6593 - 6598.PubMedGoogle Scholar
  48. Manganiello, V., Murad, F., and Vaughan, M. (1971). Effects of lipolytic and antilipolytic agents on cyclic 3′5′-adenosine. J. Biol. Chem. 246: 2195 - 2202.PubMedGoogle Scholar
  49. Manganiello, V. and Vaughan, M. (1973). An effect of insulin on cyclic adenosine 3′5′-monophosphate phosphodiesterase activity in fat cells. J. Biol. Chem. 248: 7164 - 7170.PubMedGoogle Scholar
  50. Moskowitz, J. and Fain, J.N. (1970). Stimulation by growth hormone and dexamethasone of labeled cyclic adenosine 3′5′-monophosphate accumulation by white fat cells. J. Biol. Chem. 245: 1101 - 1107.PubMedGoogle Scholar
  51. Namm, D.H. and Leader, J.P. (1974). A sensitive analytical method for the detection and quantitation of adenosine in biological samples. Anal. Biochem. 58: 511 - 524.PubMedCrossRefGoogle Scholar
  52. Olsson, R.A., Davis, C.J., Khouri, E.M., and Patterson, R.E. (1976). Evidence for an adenosine receptor on the surface of dog coronary myocytes. Circulat. Res.. 39: 93 - 98.PubMedCrossRefGoogle Scholar
  53. Paterson, A.R.P. and Oliver, J.M. (1971). Nucleoside transport. II. Inhibition by p-nitrobenzyl-thioguanosine and related compounds. Can. J. Biochem. 49: 271 - 274.PubMedCrossRefGoogle Scholar
  54. Pawlson, L.G., Lovell-Smith, C.J., Manganiello, V.C.,and Vaughan, M. (1974). Effects of epinephrine, adrenocorticotrophic hormone, and theophylline on adenosine 3′5′-monophosphate phosphodiesterase activity in fat cells. Proc. Nat. Acad. Sci. U.S.A. 71: 1639 - 1642.CrossRefGoogle Scholar
  55. Rodbell, M. (1965). Modulation of lipolysis in adipose tissue by fatty acid concentration in fat cell. Ann. N.Y. Acad. Sci. 131: 302 - 333.PubMedCrossRefGoogle Scholar
  56. Rodbell, M. (1967). Metabolism of isolated fat cells. V. Preparation of“ghosts”and their properties; adenyl cyclase and other enzymes. J. Biol. Chem. 242: 5744 - 5750.PubMedGoogle Scholar
  57. Rodbell, M. (1975). On the mechanism of activation of fat cell adenylate cyclase by guanine nucleotides. J. BioZ. Chem. 250: 5826 - 5834.Google Scholar
  58. Sakai, T., Thompson, W.J., Lavis, V.R., and Williams, R.H. (1974). Cyclic nucleotide phosphodiesterase activities from isolated fat cells: Correlation of subcellular distribution with effects of nucleotides and insulin. Arch. Biochem. Biophys. 162: 331 - 339.PubMedCrossRefGoogle Scholar
  59. Schaeffer, H.J. and Schwender, C.F. (1974). Enzyme inhibitors, 26, bridging hydrophobic and hydrophilic regions on adenosine deaminase with some 9-(2-hydroxy-3-alkyl) adenines. J. Med. Chem. 17: 6 - 8.PubMedCrossRefGoogle Scholar
  60. 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. Arch. Pharmacol. 276: 133 - 148.CrossRefGoogle Scholar
  61. Siddle, K. and Hales, C.N. (1974). The relationship between the concentration of adenosine 3′5′-cyclic monophosphate and the anti-lipolytic action of insulin in isolated rat fat-cells. Biochem. J. 142: 97 - 103.PubMedGoogle Scholar
  62. Solomon, S.S. (1975). Effect of insulin and lipolytic hormones on cyclic AMP phosphodiesterase activity in normal and diabetic rat adipose tissue. Endocrinology 96: 1366 - 1373.PubMedCrossRefGoogle Scholar
  63. Stock, K. and Prilop, M. (1974). Dissociation of catecholamineinduced formation of adenosine 3′5′-monophosphate and release of glycerol in fat cells by prostaglandin E1, E2 and N6 phenylisopropyladenosine. Arch. Pharmacol. 282: 15 - 31.CrossRefGoogle Scholar
  64. Vydelingum, N., Kissebah, A.H., Wynn, V., and Simpson, A. (1975). The role of calcium in insulin action. V. Insulin, calcium c-GMP and the regulation of protein synthesis in adipose tissue. EYiabetoZogia 11: 382 (Abstract).Google Scholar
  65. Wieser, P.B. and Fain, J.N. (1975). Insulin, prostaglandin E1, phenylisopropyladenosine and nicotinic acid as regulators of fat cell metabolism. Endocrinology 96: 1221 - 1225.PubMedCrossRefGoogle Scholar
  66. Zinman, B. and Hollenberg, C.H. (1974). Effect of insulin and lipolytic agents on rat adipocyte low Km cyclic adenosine 3′5′,-monophosphate phosphodiesterase. J. Biol. Chem. 249: 2182 - 2187.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1979

Authors and Affiliations

  • J. N. Fain
    • 1
  • R. E. Shepherd
    • 1
  1. 1.Section of Physiological Chemistry, Division of Biology and MedicineBrown UniversityProvidenceUSA

Personalised recommendations