Effect of LPS on Carbohydrate and Lipid Metabolism

  • Judy A. Spitzer
  • John J. Spitzer


Administration of endotoxin, a lipopolysaccharide (LPS) extracted from cell walls of gram-negative bacteria, elicits alterations in various metabolic parameters in many mammalian species, including man. Studies of the mechanism of metabolic alterations induced by LPS are important because release of endotoxin may contribute to the effects of sepsis, and clinical or experimental infections may alter the course of other types of trauma, shock, or injury. The overall metabolic and endocrine effects of endotoxicosis are predominantly catabolic. In general, the endocrine changes appear to be directed toward water and salt conservation, maintenance of blood pressure, and the mobilization of fuel primarily from carbohydrate stores. Eventually the breakdown of muscle protein follows, providing additional substrate for gluconeogenesis and satisfying the energy requirements of peripheral tissues and the brain.


Adipose Tissue Myocardial Blood Flow Glucose Oxidation Blood Flow Restriction Endotoxin Shock 
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  1. Adelye, A. G., Al-Fibouri, L. M., Furman, B. L., and Parratt, J. R., 1981, Endotoxin-induced metabolic changes in the conscious, unrestrained rat: Hypoglycemia and elevated blood lactate concentrations without hyperinsulinemia, Circ. Shock 8:543–550.Google Scholar
  2. Bagby, G. J., and Spitzer, J. A., 1980, Lipoprotein lipase activity in rat heart and adipose tissue during endotoxic shock, Am. J. Physiol. 238:H325–H330.PubMedGoogle Scholar
  3. Berry, L. J., 1971, Metabolic effects of bacterial endotoxin, in: Microbial Toxins, Vol. V (S. Kadis, G. Weinbaum, and S.J. Ajl, eds.), pp. 165–208, Academic Press, New York.Google Scholar
  4. Berry, L. J., Smythe, D. S., and Colwell, L. S., 1968, Inhibition of hepatic enzyme induction as a sensitive assay for endotoxin,J. Bacteriol. 96:91–99.Google Scholar
  5. Bitensky, M. W., Gorman, R. E., and Thomas, L., 1971, Selective stimulation of epinephrine-response adenyl-cyclase in mice by endotoxin, Proc. Soc. Exp. Biol. Med. 138:773.PubMedGoogle Scholar
  6. Blackard, W. G., Anderson, J. H., and Spitzer, J. J., 1976, Hyperinsulinism in endotoxin shock dogs, Metabolism 25:675–684.PubMedCrossRefGoogle Scholar
  7. Blackmore, P. F., Assimacopoulos-Jeannet, F., Chan, T. M., and Exton, J. H., 1979, Studies on a-adrenergic activation of hepatic glucose oxidation,J. Biol. Chem. 254:2828–2834.PubMedGoogle Scholar
  8. Buchanan, B. J., and Filkins, J. P., 1976, Insulin secretion and the carbohydrate metabolic alterations of endotoxemia, Circ. Shock 3:267–280.Google Scholar
  9. Cameron, G. R., Relefield, M. E., and Wilson, J., 1940, Pathological changes produced in rats and mice by a toxic fraction derived from Bacterium typhimurium, J. Pathol. Bacteriol. 51:223–233.CrossRefGoogle Scholar
  10. Chen, J. J., Babcock, D. F., and Lardy, H. A., 1978, Norepinephrine, vasopressin, glucagon and A23187 induce efflux of calcium ion from an exchangeable pool in isolated rat hepatocytes, Proc. Natl. Acad. Sci. USA 75:2234–2238.PubMedCrossRefGoogle Scholar
  11. Cline, M. J., Melmon, K. L., Davis, W. C., and Williams H. E., 1968, Mechanism of endotoxin interaction with human leukocytes, Br. J. Haematol. 15:539–547.PubMedCrossRefGoogle Scholar
  12. Cohn, Z. A., and Morse, S. I., 1960, Functional and metabolic properties of polymorphonuclear leucocytes. II. The influence of lipopolysaccharide endotoxin, J. Exp. Med. 3:689–704.CrossRefGoogle Scholar
  13. Connor, J., Fine, J., Kusano, K., McCrea, M. J., Parnas, I., and Prosser, C. L., 1973, Potentiation by endotoxin of responses associated with increases in calcium conductance, Proc. Natl. Acad. Sci. USA 70:3301–3304.PubMedCrossRefGoogle Scholar
  14. Ferguson, J. L., Spitzer, J. J., and Miller, H. I., 1978, Effects of endotoxin on regional blood flow in the unanesthetized guinea pig, J. Surg. Res. 23:236–243.CrossRefGoogle Scholar
  15. Filkins, J. P., and Buchanan, B. J., 1977, In vivo vs in vitro effects of endotoxin on glycogenosis, gluconeogenesis and glucose utilization, Proc. Soc. Exp. Biol. Med. 155:216–218.PubMedGoogle Scholar
  16. Filkins, J. P., and Cornell, R. P., 1974, Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxic shock, Am. J. Physiol. 227:778–782.PubMedGoogle Scholar
  17. Filkins, J. P., and Figlewicz, D. P., 1979, Increased insulin responsiveness in endotoxico-sis, Circ. Shock 6:1–6.PubMedGoogle Scholar
  18. Fredholm, B. B., 1971, The effect of lactate in canine subcutaneous adipose tissue in situ, Acta Physiol. Scand. 81:110–123.CrossRefGoogle Scholar
  19. Gartner, S. L., 1975, Hepatic levels of cyclic AMP in normal and lead-sensitized rats after treatment with bacterial endotoxin, Experientia 31:566.PubMedCrossRefGoogle Scholar
  20. Gimpel, L., Hodgins, D. S., and Jacobson, E. D., 1974, Effects of endotoxin on hepatic adenylate cyclase activity, Circ. Shock 1:21.Google Scholar
  21. Hamosh, M., and Shapiro, B., 1960, The mechanism of glycogenolytic action of endotoxin, Br. J. Exp. Pathol. 41:372.PubMedGoogle Scholar
  22. Hikawyj-Yevich, I., and Spitzer, J. A., 1977, The role of adrenergic receptors and Ca2+ in the action of endotoxin on human fat cells,J. Surg. Res. 23:233–238.PubMedCrossRefGoogle Scholar
  23. Hinshaw, L. B., Archer, L. T., Beller, B. K., White, G. L., Schroeder, T. M., and Holmes, D. D., 1977, Glucose utilization and role of blood in endotoxin shock, Am. J. Physiol. 233:E71–E79.PubMedGoogle Scholar
  24. Holley, D. C., and Spitzer, J. A., 1980, Insulin action and binding in adipocytes exposed to endotoxin in vitro and in vivo, Circ. Shock 7:3–13.Google Scholar
  25. Issekutz, B., Jr., Miller, H. I., Paul, P., and Rodahl, K., 1965, Effect of lactic acid on free fatty acids and glucose oxidation in dogs, Am. J. Physiol. 209:1137–1144.PubMedGoogle Scholar
  26. Kelleher, D. L., Gagby, G. J., and Spitzer, J. J., 1981, Metabolic and endocrine alterations following endotoxin administration in normal and diabetic rats, in: Advances in Physiological Sciences, Vol. 26 (Z. Biro, A. G. B. Kovach, J. J. Spitzer, and H. B. Stoner, eds.), pp. 181–189, Pergamon Press/Akademiai Kiado, Budapest.Google Scholar
  27. Kelleher, D. L., Bagby, G. J., Fong, B. C., and Spitzer, J. J., 1982, Glucose turnover 5 hours following endotoxin administration to normal and diabetic rats, Metabolism 31:252–257.PubMedCrossRefGoogle Scholar
  28. Kinney, J. M., and Felig, P., 1979, The metabolic response to injury and infection, in: Endocrinology (L.J. DeGroot, ed.), pp. 1963–1985, Grune & Stratton, New York.Google Scholar
  29. Kovach, A. G. B., Kovach, E., Sandor, P., Spitzer, J. A., and Spitzer, J. J., 1976, Metabolic responses to localized ischemia in adipose tissue, J. Surg. Res. 20:37–44.PubMedCrossRefGoogle Scholar
  30. Kuttner, R., and Spitzer, J. J., 1978, Gluconeogenesis from alanine in endotoxin-treated dogs,J. Surg. Res. 25:166.PubMedCrossRefGoogle Scholar
  31. Landy, M., Whitby, J. L., Michale, J. G., Woods, M. W., and Newton, W. L., 1962, Effect of bacterial endotoxin in germ free mice, Proc. Soc. Exp. Biol. Med. 109:352–356.PubMedGoogle Scholar
  32. LaNoue, K., Mason, A. D., Jr., and Daniels, J., 1968, The impairment of gluconeogenesis by gram negative infection, Metabolism 17:606–611.PubMedCrossRefGoogle Scholar
  33. Leach, G. J., and Spitzer, J. A., 1981, Endotoxin induced alterations in glucose transport in isolated adipocytes, Biochim. Biophys. Acta 648:71–79.PubMedCrossRefGoogle Scholar
  34. Little, J. R., Goto, M., and Spitzer, J. J., 1970, Effect of ketones on metabolism on FFA by dog myocardium and skeletal muscle, Am. J. Physiol. 219:1458–1463.PubMedGoogle Scholar
  35. Liu, M.-S., and Spitzer, J. J., 1977, Myocardial fatty acid and lactate kinetics after E. coli endotoxin administration, Circ. Shock 4:191–200.PubMedGoogle Scholar
  36. Liu, M.-S., Long, W. M., and Spitzer, J. J., 1981, Influence of E. coli endotoxin on palmi-tate, glucose and lactate utilization by isolated dog heart myocytes, in: The Pathology of Endotoxin at the Cellular Level (J. A. Majda and R. J. Person, eds.), pp. 115–121, Liss, New York.Google Scholar
  37. McDonald, J. M., Burns, D. E., and Jarett, L., 1978, Ability of insulin to increase calcium uptake by adipocyte endoplasmic reticulum,J. Biol. Chem. 253:3504–3508.PubMedGoogle Scholar
  38. Martin, S. P., McKinney, G. R., and Green, R., 1955, The metabolism of human polymorphonuclear leukocytes, Ann. N.Y. Acad. Sci. 59:996–1002.PubMedCrossRefGoogle Scholar
  39. Menten, M. L., and Manning, H. M., 1924, Blood sugar studies on rabbits injected with organisms of the enteritidis-parathyroid B group,J. Med. Res. 44:676–681.Google Scholar
  40. Merrill, G. F., and Spitzer, J. J., 1978, Glucose and lactate kinetics in guinea pigs following Escherichia coli endotoxin administration, Circ. Shock 5:11–21.PubMedGoogle Scholar
  41. Motsay, G. J., Alho, A. V., Dietzmann, R. H., and Lillehei, R. C., 1971, Pathophysiology and therapy of endotoxin (septic) shock, in: Emergency Medical Management (S. Spitzer, W. W. Oaks, and J. H. Moyer, eds.), pp. 247–267, Grune & Stratton, New York.Google Scholar
  42. Neufeld, H. A., Pace, J. A., and White, F. E., 1976, The effect of bacterial infections on ketone concentrations in rat liver and blood and on free fatty acid concentrations in rat blood, Metabolism 25:877–884.PubMedCrossRefGoogle Scholar
  43. Nicolas, G. G., Mela, L. M., and Miller, L. D., 1972, Shock-induced alterations of mitochondrial membrane transport, Ann. Surg. 176:579–584.CrossRefGoogle Scholar
  44. Person, R. J., 1977, Endotoxin alters spontaneous transmitter release at frog neuromuscular junction, J. Neurosa. Res. 3:63–72.CrossRefGoogle Scholar
  45. Rayfield, E. J., Curnow, R. T., Reinhard, D., and Kochiceril, N. M., 1977, Effects of acute endotoxemia on glucoregulation in normal and diabetic subjects,J. Clin. Endocrinol. Metab. 45:513–521.PubMedCrossRefGoogle Scholar
  46. Raymond, R. M., Harkema, J. M., and Emerson, T. E., Jr., 1981, Mechanism of increased glucose uptake by skeletal muscle during E. coli endotoxin shock in the dog, Circ. Shock 8:77–93.PubMedGoogle Scholar
  47. Ribi, E., Haskins, W. T., Landry, M., and Milner, K. C., 1961, Symposium on bacterial endotoxin. I. Relationship of chemical composition to biological activity, Bacteriol. Rev. 25:427–436.PubMedGoogle Scholar
  48. Romanosky, A. J., Bagby, G. J., Bockman, E. L., and Spitzer, J. J., 1980a, Increased skeletal muscle glucose uptake and lactate release following E. coli endotoxin administration, Am. J. Physiol. 239:E311–E316.PubMedGoogle Scholar
  49. Romanosky, A. J., Bagby, G. J., Bockman, E. L., and Spitzer, J. J., 1980b, Free fatty acid utilization by skeletal muscle after endotoxin administration, Am. J. Physiol. 239:E391–E395.PubMedGoogle Scholar
  50. Romanosky, A. J., McGuinness, O., and Spitzer, J. J., 1982, Ketone body (KB) clearance following endotoxin (ET) administration in dogs, Fed. Proc. 41:1133.Google Scholar
  51. Schimmel, R. J., 1975, The role of calcium ion in epinephrine activation of lipolysis, Horm. Metab. Res. 8:195–201.CrossRefGoogle Scholar
  52. Scholl, R. A., Lang, C. H., Spitzer, J. J., and Bagby, G. J., 1982, Tissue lipoprotein lipase (LPL) activities in rats challenged with endotoxin, live E. coli, or peritonitis, Fed. Proc. 41:1134.Google Scholar
  53. Scott, J. C., Weng, J. T., and Spitzer, J. J., 1973, Myocardial metabolism during endotoxic shock, in: Neurohumoral and Metabolic Aspects of Injury (A. G. B. Kovach, B. Stoner, and J. J. Spitzer, eds.), pp. 375–386, Plenum Press, New York.Google Scholar
  54. Shands, P. W., Jr., Miller, W., Martin, H., and Senterfilt, V., 1969, Hypoglycemic activity of endotoxin. II. Mechanism of the phenomenon in BCG-infected mice, J. Bacteriol. 98:495–501.Google Scholar
  55. Snyder, J. S., Deters, M., and Ingle, J., 1971, Effect of endotoxin on pyruvate kinase activity in mouse liver, Infect. Immun. 4:138–142.PubMedGoogle Scholar
  56. Soulsby, M. E., Bruin, F. D., Looney, T. J., and Hess, M. L., 1978, Influence of endotoxin on myocardial calcium transport and the effect of augmented venous return, Circ. Shock 5:23–34.PubMedGoogle Scholar
  57. Spitzer, J. A., 1974, Endotoxin-induced alterations in isolated fat cells: Effect on norepinephrine-stimulated lipolysis and cyclic 3′5′-adenosine monophosphate accumulation, Proc. Soc. Exp. Biol. Med. 145:186–191.PubMedGoogle Scholar
  58. Spitzer, J. A., 1981, Altered insulin sensitivity in endotoxin and septic shock, in: Advances in Physiological Sciences, Vol. 26 (Z. Biro, A. G. B. Kovach, J. J. Spitzer, and H. B. Stoner, eds.), pp. 143–150, Pergamon Press/Akademiai Kiado, Budapest.Google Scholar
  59. Spitzer, J. A., and Holley, D. C., 1979, Alterations in insulin action by endotoxin in vitro, in: Advances in Shock Research, Vol. 2 (W. Schumer, J. J. Spitzer, and B. E. Marshall, eds.), pp. 129–136, Liss, New York.Google Scholar
  60. Spitzer, J. A., Archer, L., Greenfield, L. J., Hinshaw, L. B., and Spitzer, J. J., 1972, Metabolism of the nonhepatic splanchnic area in baboons and the effects of endotoxin, Proc. Soc. Exp. Biol. Med. 141:21–25.PubMedGoogle Scholar
  61. Spitzer, J. A., Kovach, A. G. B., Sandor, P., Spitzer, J. J., and Storck, R., 1973a, Adipose tissue and endotoxin shock, Acta Physiol. Acad. Sci. Hung. 44:183–194.PubMedGoogle Scholar
  62. Spitzer, J. A., Kovach, A. G. B., Roseli, S., Sandor, P., Spitzer, J. J., and Storck, R., 1973b, Influence of endotoxin on adipose tissue metabolism, in: Advances in Experimental Medicine and Biology, Vol. 33 (A. G. B. Kovach, H. B. Stoner, and J. J. Spitzer, eds.), pp. 337–344, Plenum Press, New York.Google Scholar
  63. Spitzer, J. J., 1979, Lipid metabolism in endotoxic shock, Circ. Shock 1(Suppl.):69–79.Google Scholar
  64. Spitzer, J. J., 1981, Lactate-fatty acid competition in the heart during shock, in: Advances in Physiological Sciences, Vol. 8 (A. G. B. Kovach, E. Monos, and G. Rubanyi, eds.), pp. 175–178, Pergamon Press/Akademiai Kiado, Budapest.Google Scholar
  65. Spitzer, J. J., Bechtel, A. A., Archer, L. T., Black, M. R., and Hinshaw, L. B., 1974, Myocardial substrate utilization in dogs following endotoxin administration, Am. J. Physiol. 227:132–136.PubMedGoogle Scholar
  66. Spitzer, J. J., Ferguson, J. L., Hirsch, H. J., Loo, S., and Gabbay, K. W., 1980, Effects of E. coli endotoxin on pancreatic hormones and blood flow, Circ. Shock 7:353–360.PubMedGoogle Scholar
  67. Vydelingum, N., Kissebah, A. H., and Wijn, V., 1978, Importance of cyclic guanosine 3′5′-monophosphate and calcium ions in insulin stimulation of lipoprotein lipase activity and protein synthesis in adipose tissue, Horm. Metab. Res. 10:38–46.PubMedCrossRefGoogle Scholar
  68. Witek-Janusek, L., and Filkins, J. P., 1981, Insulin-like action of endotoxin: Antagonism by steroidal and non-steroidal anti-inflammatory agents, Circ. Shock 8:573–583.PubMedGoogle Scholar
  69. Wolfe, R. R., Elahi, D., and Spitzer, J. J., 1977a, Glucose and lactate kinetics after endotoxin administration in dogs, Am. J. Physiol. 232:E180–E185.PubMedGoogle Scholar
  70. Wolfe, R. R., Elahi, D., and Spitzer, J. J., 1977b, Glucose kinetics in dogs following a lethal dose of endotoxin, Metabolism 26:847–850.PubMedCrossRefGoogle Scholar
  71. Woods, M. W., Burke, D., Howard, T., and Landy, M., 1961, Insulin-like action of endotoxins in normal and leukemic leukocytes and other tissues, Proc. Am. Assoc. Cancer Res. 3:279.Google Scholar
  72. Woods, M. W., Landy, M., Burke, D., and Howard, T., 1964, Effect of endotoxin on cellular metabolism, in: Bacterial Endotoxins (M. Landy and W. Braun, eds.), pp. 160–181. Rutgers University Press, New Brunswick, N.J.Google Scholar
  73. Zenser, T. V., DeRobertis, F. R., George, D. T., and Rayfield, E. J., 1974, Infection-induced hyperglucagonemia and altered hepatic response to glucagon in the rat, Am. J. Physiol. 227:1299–1305.PubMedGoogle Scholar
  74. Zwadyk, P., Jr., and Snyder, L. S., 1973a, Effects of endotoxin on hepatic glycogen metabolism in vitro, Proc. Soc. Exp. Biol. Med. 142:299.PubMedGoogle Scholar
  75. Zwadyk, P., Jr., and Snyder, L. S., 1973b, Effects of endotoxin on glycogenolytic enzymes of mouse liver, Proc. Soc. Exp. Biol. Med. 143:864–868.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Judy A. Spitzer
    • 1
  • John J. Spitzer
    • 1
  1. 1.Department of PhysiologyLouisiana State University Medical CenterNew OrleansUSA

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