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Acute effects of endotoxin (lipopolysaccharide) on tissue lipid metabolism in the lactating rat. The role of delivery of intestinal glucose

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Abstract

The aim of this study was to compare the effects of endotoxin on lipid metabolism and, in particular, lipogenesis in virgin and lactating rats. Intraperitoneal administration of bacterial endotoxin (lipopolysaccharide, LPS; 3 mg/kg body wt.) to fed virgin rats caused a 4-fold increase in lipogenic rate in liverin vivo. The stimulatory effect was not seen when glucose (6 mmol) was administered either orally or intraperitoneally to increase the basal rate. In contrast, the rate of lipogenesis in interscapular brown adipose tissue was inhibited, after LPS, and this was relieved by intraperitoneal glucose. In the lactating rat there were no significant changes in hepatic lipogenesis after the administration of endotoxin. However, LPS decreased the lipogenic rate in mammary gland of lactating rats and intraperitoneal glucose administration, but not oral, was able to restore the rate. In both virgin and lactating rats, LPS decreased glucose removal from the intestina tract. In lactating rats, LPS induced a rise in blood concentrations of lactate, and plasma triacylglycerols and non-esterified fatty acids, similar to those in endotoxin-treated virgin rats. The administration of LPS did not decrease the accumulation of radioactivity in lipid in either liver or in mammary gland after injection of3H-oleate. In contrast, LPS decreased the accumulation of radioactivity in mammary gland after injection of2H-chylomicrons and increased it in liver and plasma. These changes were accompanied by a decrease in mammary gland activity of lipoprotein lipase. Intraperitoneal glucose partially reversed these changes in chylomicron disposition. It is concluded that the inhibitory effect of LPS on mammary gland lipogenesis and uptake of exogenous lipid is primarily due to sensitivity of this tissue to the rate of delivery of glucose from the intestine.

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References

  1. Beisel WR: Metabolic response to infection. Annu Rev Med26:9–20, 1975

    Google Scholar 

  2. Goldstein SA, Elwyn DH: The effects of injury and sepsis on fuel utilization. Annu Rev Nutr 9: 445–473, 1989

    Google Scholar 

  3. Kaufmann RL, Matson CF, Beisel WR: Hypertriglyceridemia produced by endotoxin: role of impaired triglyceride disposal mechanisms. J Infect Dis 133: 548–555, 1976

    Google Scholar 

  4. Guckian JD: Role of metabolism in pathogenesis of bacteremia due toDiplococcus pneumoniae in rabbits. J Infect Dis 127: 1–8, 1973

    Google Scholar 

  5. Wolfe RR, Shaw JHF, Durkot MJ: Effects of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. Am J Physiol 248: E732-E740, 1985

    Google Scholar 

  6. Agius L, Robinson AM, Girard JR, Williamson DH: Alterations in the rate of lipogenesisin vivo in maternal liver and adipose tissue on premature weaning of lactate rats. Biochem J 180:689–692, 1979

    Google Scholar 

  7. Flint DJ, Clegg RA, Vernon RG: Prolactin and the regulation of adipose tissue metabolism during lactation in rats. Mol Cell Endocrinol 22:265–275, 1981

    Google Scholar 

  8. Oller do Nascimento CM, Williamson DH: Evidence for conservation of dietary lipid in the rat during lactation and the immediate period after removal of the litter. Biochem J 239: 233–236, 1986

    Google Scholar 

  9. Williamson DH: Regulation of metabolism during lactation in the rat. Reprod Nutr Dev 26:597–603, 1986

    Google Scholar 

  10. Robinson AM, Girard JR, Williamson DH: Evidence for a role of insulin in the regulation of lipogenesis in lactating rat mammary gland. Biochem J 176:343–346, 1978

    Google Scholar 

  11. Adi S, Pollock AS, Shigenaga JK, Moser AH, Feingold KR, Grunfeld C: Role for monokines in the metabolic effects of endotoxin. Interferon-γ restores responsiveness of C3H/HeJ micein vivo. J Clin Invest 89: 1603–1609, 1992

    Google Scholar 

  12. Feingold KR, Staprans I, Memon RA et al.: Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production white high doses inhibit clearance. J Lipid Res 33: 1765–1776, 1990

    Google Scholar 

  13. Stansbie D, Brownsey RM, Crettaz M, Denton RM: Acute effectsin vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Biochem J 160: 413–416, 1976

    Google Scholar 

  14. Good CA, Kramer H, Somogyi M: The determination of glycogen. J Biol Chem 100: 485–494, 1933

    Google Scholar 

  15. Postle AD, Bloxham DO: The use of tritiated water to measure absolute rates of hepatic glycogen synthesis. Biochem J 192: 65–73, 1980

    Google Scholar 

  16. Keppler D, Decker K: Glycogen. In: H.U. Bergneyer (ed). Methods of Enzymatic Analysis, Vol VI. Academic Press, Weinheim, 1984, pp 11–18

    Google Scholar 

  17. Slein MW: D-glucose determination with hexokinase and glucose-6-phosphate dehydrogenase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, London, 1963, pp 117–123

    Google Scholar 

  18. Hohorst HJ, Kreutz FH, Bücher T: On the metabolite content and the metabolite concentration in the liver of the rat. Biochem Z 332: 18–46, 1959

    Google Scholar 

  19. Eggstein M, Kreutz FH: A new method for the determination of neutral fats in blood serum and tissues. Klin Wochenschr 44: 262–267, 1966

    Google Scholar 

  20. Albano JDM, Ekins RP, Maritz G, Turner RC: A sensitive precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol 70: 487–509, 1972

    Google Scholar 

  21. Lang G, Michal G: D-glucose-6-phosphate and D-fructose-6-phosphate, In: H.U. Bergmeyer (ed) Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1238–1242

    Google Scholar 

  22. Lamprecht W, Trautschold I: Adenosine-5′-triphosphate. Determination with hexokinase and glucose-6-phosphate dehydrogenase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, London, 1963, pp 543–551

    Google Scholar 

  23. Mellanby J, Williamson DH: Acetoacetate. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1840–1843

    Google Scholar 

  24. Williamson DH, Mellanby J: 3-Hydroxybutyrate. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1836–1839

    Google Scholar 

  25. Bezman-Tarcher A, Otway S, Robinson DS: The removal of triglyceride fatty acids from the incubation of the supradiaphragmatic portion of the rat. Proc Roy Soc B 162: 411–426, 1965

    Google Scholar 

  26. Nilsson-Ehle P Schotz MC: A stable radioactive substrate emulsion for assay of lipoprotein lipase. J Lipid Res 17: 536–541, 1976

    Google Scholar 

  27. Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H: Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 250: E634-E640, 1986

    Google Scholar 

  28. Argilés JM, López-Soriano FJ, Evans RD, Williamson DH: Interleukin-1 and lipid metabolism in the rat. Biochem J 259: 673–678, 1989

    Google Scholar 

  29. Arbós J, López-Soriano FJ, Carbó N Argilés JM: Effects of tumour mecrosis factor-α (cachectin) on glucose metabolism in the rat. Mol Cell Biochem 112: 53–59, 1992

    Google Scholar 

  30. Mercer SW, Williamson DH: The regulation of lipogenesisin vivo in the lactating mammary gland to the rat during the starved-re-fed transition. Studies with acarbose, a glucosidase inhibitior. Biochem J 242: 235–243, 1987

    Google Scholar 

  31. Williamson DH, Ilic V, Jones RG: Evidence that the stimulation of lipogenesis in the mammary glands of starved lactating rats re-fed with a chow diet is dependent on continued hepatic gluconeogenesis during the absorptive period. Biochem J 228: 727–733, 1981

    Google Scholar 

  32. Bizzi A, Tacconi MT, Garrattini S: Lowering of blood ketone bodies induced by drugs preventing free fatty acid mobilization. Experientia 22: 664–666, 1966

    Google Scholar 

  33. Feingold KR, Adi S, Staprans I et al.: Diet affects the mechanism by which TNF stimulates hepatic triglyceride production. Am J Physiol 259: E177-E184, 1990

    Google Scholar 

  34. Robinson AM, Williamson DH: Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev 60: 143–187, 1980

    Google Scholar 

  35. Van Deuren M, Dofferhoff ASM, Van der Meer JWM: Cytokines and the response to infection. J Pathol 168: 349–356, 1992

    Google Scholar 

  36. Grunfeld C, Feingold KR: Tumor necrosis factor, cytokines, and the hyperlipidemia of infection. Trends Endocrinol Metab 2: 213–219, 1991

    Google Scholar 

  37. Feingold KR, Mounzer S, Serio MK, Moser AH, Dinarello CA, Grunfeld K: Multiple cytokines stimulate hepatic lipid synthesisin vivo. Endocrinology 125: 267–274, 1989

    Google Scholar 

  38. de Vasconcelos PRL, Kettlewell MGW, Gibbons GF, Williamson DH: Increased rates of hepatic cholesterogenesis and fatty acid synthesis in septic ratsin vivo: evidence for the possible involvement of insulin. Clin Sci 76: 267–274, 1989

    Google Scholar 

  39. Beutler B, Cerami A: Tumor necrosis, cachexia, shock, and inflammation: a common mediator. Annu Rev Biochem 57: 505–518, 1988

    Google Scholar 

  40. Agius L, Williamson DH: Lipogenesis in interscapular brown adipose tissue in virgin, pregnant and lactating rats. The effects of intragastric feeding. Biochem J 190: 477–480, 1980

    Google Scholar 

  41. Cripps AW, Williams VJ: The effect of pregnancy and lactation on food intake, gastrointestinal anatomy and the absorptive capacity of the small intestine in the albino rat. Brit J Nutr 33: 17–32, 1975

    Google Scholar 

  42. Evans RD, Williamson DH: Tumor necrosis factor-α (cachectin) mimics some of the effects of tumour growth on the disposal of a [14C]lipid load in virgin, lactating and litter-removed rats. Biochem J 256: 1055–1058, 1988

    Google Scholar 

  43. Williamson DH: The lactating mammary gland of the rat and the starved-re-fed transition: a model system for the study of the temporal regulation of substrate utilization. Biochem Soc Trans 18: 853–856, 1990

    Google Scholar 

  44. Threadgold LC, Kuhn NJ: Monosaccharide transport in the mammary gland of the intact lactating rat. Biochem J 218: 213–219, 1984

    Google Scholar 

  45. Burnol A-F, Leturque A, Loizeau M, Postic C, Girard J: Glucose transporter expression in rat mammary gland. Biochem J 270: 277–279, 1990

    Google Scholar 

  46. Oller do Nascimento CM, Williamson DH: Tissue-specific effects of starvation and refeeding on the disposal of oral [1-14C]triolein in the rat during lactation and on removal of litter. Biochem J 254: 539–546, 1988

    Google Scholar 

  47. Da Costa THM, Williamson DH: Effects of exogenous insulin of vanadate on disposal of dietary triacylglycerols between mammary gland and adipose tissue in the lactating rat: insulin resistance in white adipose tissue. Biochem J 290: 557–561, 1993

    Google Scholar 

  48. Da Costa THM, Williamson DH: Regulation of rat mammary-gland uptake of orally administered [1-14C]triolein by insulin and prolactin: evidence for bihormonal control of lipoprotein lipase activity. Biochem J 300: 257–262, 1994

    Google Scholar 

  49. Page T: Evidence for the involvement of a gastrointestinal peptide in the regulation of glucose uptake in the mammary gland of the lactating rat. Biochem J 258: 639–643, 1989

    Google Scholar 

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Authors and Affiliations

  1. Departament de Bioquimica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08071, Barcelona, Spain

    Francisco J. López-Soriano

  2. Metabolic Research Laboratory, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Woodstock Road, OX2 6HE, Oxford, UK

    Dermot H. Williamson

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  1. Francisco J. López-Soriano
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  2. Dermot H. Williamson
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López-Soriano, F.J., Williamson, D.H. Acute effects of endotoxin (lipopolysaccharide) on tissue lipid metabolism in the lactating rat. The role of delivery of intestinal glucose. Mol Cell Biochem 141, 113–120 (1994). https://doi.org/10.1007/BF00926174

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  • DOI: https://doi.org/10.1007/BF00926174

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