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Metabolic effects of tumour necrosis factor-α on rat brown adipose tissue

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Abstract

Intravenous administration of a single dose (100 μg/kg bw) of recombinant tumour necrosis factor-α (TNF, cachectin) to rats increased the rate ofin vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue.

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References

  1. Lawson DH, Richmond A, Nixon DW, Rudman D: Metabolic approaches to cancer cachexia. Annu Rev Nutr 2: 227–301, 1982

    Google Scholar 

  2. Brooks SL, Neville AM, Rothwell NJ, Stock MJ, Wilson S: Sympathetic activation of brown adipose tissue thermogenesis in cachexia. Biosci Rep 1: 509–517, 1981

    PubMed  Google Scholar 

  3. Llovera M, Lopez-Soriano FJ, Argiles JM: Effects of tumor necrosis factor-α on muscle-protein turnover in female Wistar rats. J Natl Cancer Inst 85: 1334–1339, 1993

    PubMed  Google Scholar 

  4. Costelli P, Carbo N, Tessitore L, Bagby GJ, Lopez-Soriano FJ, Baccino FM, Argiles JM: Tumour necrosis factor-α mediates changes in tissue protein turnover in a rat cancer cachexia model. J Clin Invest 92: 2783–2789, 1993

    PubMed  Google Scholar 

  5. Evans RD, Argiles JM, Williamson DH: Metabolic effects of tumour necrosis factor-α (cachectin) and interleukin-1. Clin Sci 77: 357–364, 1989

    PubMed  Google Scholar 

  6. Semb H, Peterson J, Tavernier J, Olivecrona T: Multiple effects of tumour necrosis factor on lipoprotein lipasein vivo. J Biol Chem 262: 8390–8394, 1987

    PubMed  Google Scholar 

  7. Evans RD, Williamson DH: Tumour 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

    PubMed  Google Scholar 

  8. Price SR, Olivecrona T, Pekala PH: Regulation of lipoprotein lipase synthesis by recombinant tumour necrosis factor. The primary regulatory role of the hormone in 3T3-L1 adipocytes. Arch Biochem Biophys 251: 738–746, 1986

    PubMed  Google Scholar 

  9. Kawakami M, Murase T, Ogawa H, Ishibashi S, Mori N, Takaku F, Shibata S: Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3-L1 adipocytes. J Biochem 101: 331–338, 1987

    PubMed  Google Scholar 

  10. Feingold KR, Grunfeld C: Tumor necrosis factor-α stimulates hepatic lipogenesis in the ratin vivo. J Clin Invest 80: 184–190, 1987

    PubMed  Google Scholar 

  11. Feingold KR, Serio MK, Adi S, Moser AH, Grunfeld C: Multiple cytokines stimulate hepatic lipid synthesisin vivo. Endocrinology 124: 2336–2342, 1989

    PubMed  Google Scholar 

  12. Chajek-Shaul T, Friedman G, Stein O, Shiloi E, Etienne J, Stein Y: Mechanism of the hypertriglyceridemia induced by tumor necrosis factor administration to rats. Biochim Biophys Acta 1001: 316–324, 1989

    PubMed  Google Scholar 

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

    Google Scholar 

  14. Evans DA, Jacobs DO, Wilmore DW: Tumor necrosis factor enhances glucose uptake by peripheral tissues. Am J Physiol 257:R1182-R1189, 1989

    PubMed  Google Scholar 

  15. Warren WS, Donner DB, Starnes HF Jr, Brennan MF: Modulation of endogenous hormone action by recombinant human necrosis factor. Proc Natl Acad Sci USA 84: 8619–8622, 1987

    PubMed  Google Scholar 

  16. Argiles JM, Lopez-Soriano FJ, Wiggins D, Williamson DH: Comparative effects of tumour necrosis factor-α (cachectin), interleukin-1-β and tumour growth on amino acid metabolism in the ratin vivo. Biochem J 261: 357–362, 1989

    PubMed  Google Scholar 

  17. Argiles JM, Lopez-Soriano FJ: The effects of tumour necrosis factor-α (cachectin) and tumour growth on hepatic amino acid utilization. Biochem J 266: 123–126, 1990

    PubMed  Google Scholar 

  18. Argiles JM, Garcia-Martinez C, Llovera M, Lopez-Soriano FJ: The role of cytokines in muscle wasting: its relation with cancer cachexia. Med Res Rev 12: 637–652, 1992

    PubMed  Google Scholar 

  19. Foster DO, Frydman ML: Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Can J Physiol Pharmacol 56: 110–122, 1978

    PubMed  Google Scholar 

  20. Rothwell NJ, Stock MJ: A role for brown adipose tissue in diet-induced thermogenesis. Nature 281: 31–35, 1979

    PubMed  Google Scholar 

  21. Prusiner SB, Cannon B, Lindberg O: Oxidative metabolism in cells isolated from brown adipose tissue. 1. Catecholamine and fatty acid stimulation of respiration. Eur J Biochem 6: 15–22, 1968

    PubMed  Google Scholar 

  22. Carneheim C, Nedergaard J, Cannon B: Beta-adrenergic stimulation of lipoprotein lipase in brown adipose tissue during acclimation to cold. Amer J Physiol 246: E327-E333, 1984

    PubMed  Google Scholar 

  23. Ferre P, Burnol AF, Leturque A, Terretaz J, Penicaud L, Jeanenaud B, Girard J: Glucose utilizationin vivo and insulin-sensitivity of rat brown adipose tissue in various physiological and pathological conditions. Biochem J 233: 249–252, 1986

    PubMed  Google Scholar 

  24. Agius L, Williamson DH: The utilization of ketone bodies by the interscapular brown adipose tissue of the rat. Biochim Biophys Acta 666: 127–132, 1981

    PubMed  Google Scholar 

  25. Lopez-Soriano FJ, Fernandez-Lopez JA, Mampel T, Villarroya F, Iglesias R, Alemany M: Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation. Biochem J 252: 843–849, 1988

    PubMed  Google Scholar 

  26. Coombes RC, Rothwell NJ, Shah P, Stock MJ: Changes in thermogenesis and brown fat activity in response to tumour necrosis factor in the rat. Biosci Rep 7: 791–799, 1987

    PubMed  Google Scholar 

  27. Rothwell NJ: Central effects of TNF-α on thermogenesis and fever in the rat. Biosci Rep 8: 345–352, 1988

    PubMed  Google Scholar 

  28. Lopez-Soriano FJ, Alemany M: Effect of alanine onin vitro glucose utilization by interscapular brown adipose tissue. Biochim Biophys Acta 1010: 338–341, 1989

    PubMed  Google Scholar 

  29. Lopez-Soriano FJ, Alemany M:In vitro alanine utilization by rat interscapular brown adipose tissue. Biochim Biophys Acta 1036: 6–10, 1990

    PubMed  Google Scholar 

  30. Umbreit WW, Burris RH, Stauffer SF: In Manometric Techniques. Burguess Publ Co, Minneapolis, 1964, p 132

    Google Scholar 

  31. Stansbie D, Brownsey RW, 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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  33. Eggstein M, Kuhlmann E: Triglycerides and glycerol. Determination after alkaline hydrolysis. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1825–1831

    Google Scholar 

  34. Wollenberger A, Ristau O, Schoffa G: Ein einfache techknic der extrema schnellen abkuhlung groberer gewebestueke. Pflügers Arch Gesamte Physiol Menschen Tiere 270: 399–412, 1960

    Google Scholar 

  35. Jamdar SC, Greengard O: Premature formation of glucokinase in developing rat liver. J Biol Chem 245: 2779–2783, 1970

    PubMed  Google Scholar 

  36. Shonk CE, Boxer GE: Enzyme patterns in human tissues. I. Methods for the determination of glycolytic enzymes. Cancer Res 24: 709–721, 1964

    PubMed  Google Scholar 

  37. Bergmeyer HU, Bernt E: Glutamate-pyruvate transaminase. UV-assay, manual method. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 752–758

    Google Scholar 

  38. Majerus PW, Jacobs R, Smith MB, Morris HP: The regulation of fatty acid biosynthesis in rat hepatomas. J Biol Chem 243: 3588–3595, 1968

    PubMed  Google Scholar 

  39. Lynen F: Fatty acid synthesis from malonil-CoA. In: S.P. Colowick and N.O. Kaplan (eds). Methods in Enzymology, vol 5. Academic Press, New York-London, 1962, pp 443–451

    Google Scholar 

  40. Greengard O, Jamdar SC: The prematurely promoted formation of liver enzymes in suckling rats. Biochim Biophys Acta 237: 476–483, 1971

    PubMed  Google Scholar 

  41. Lowry OH, Rosebrough N, Farr A, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  42. 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 

  43. Williamson DH: L-alanine. Determination with alanine dehydrogenase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1679–1682

    Google Scholar 

  44. Dagley S: Citrate. UV spectrophotometric determination. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1562–1565

    Google Scholar 

  45. Warren RS, Starnes HF, Alcock N, Calvano S, Brennan MF: Hormonal and metabolic response to recombinant human tumor necrosis factor. Am J Physiol 255: E206-E212, 1988

    PubMed  Google Scholar 

  46. Cornelius P, Marlowe M, Lee MD, Pekala PH: The growth factor-like effects of tumor necrosis factor-α. Stimulation of glucose transport activity and induction of glucose transporter and immediate early gene expression in 3T3-L1 preadipocytes. J Biol Chem 265: 20506–20616, 1990

    PubMed  Google Scholar 

  47. Stein O, Shiloni E, Stein Y: Effect of TNF on triacylglycerol in cultured vascular smooth muscle cells. Biochim Biophys Acta 1082: 33–36, 1991

    PubMed  Google Scholar 

  48. Arbos J, Lopez-Soriano FJ, Carbo N, Argiles JM: Effects of tumour necrosis factor-α (cachectin) on glucose metabolism in the rat. Intestinal absorption and isolated enterocyte metabolism. Molec Cell Biochem 112: 53–59, 1992

    PubMed  Google Scholar 

  49. Krauss RM, Grunfeld C, Doerrler WT, Feingold KR: Tumor necrosis factor acutely increases plasma levels of very low density lipoproteins of normal size and composition. Endocrinology 127: 1016–1021, 1990

    PubMed  Google Scholar 

  50. Lopez-Soriano J, Argiles JM, Lopez-Soriano FJ: Effects of tumour necrosis factor-α on the enzymatic activities related to glucose metabolism. Biochem Molec Biol Int 30: 21–27, 1993

    PubMed  Google Scholar 

  51. Yasmineh WG, Theologides A: Effect of tumor necrosis factor on enzymes of gluconeogenesis in the rat. Proc Soc Exptl Biol Med 199: 97–103, 1992

    Google Scholar 

  52. Lopez-Soriano FJ, Alemany M: Effect of cold-temperature exposure and acclimation on amino acid pool changes and enzyme activities of rat brown adipose tissue. Biochim Biophys Acta 925: 265–271, 1987

    PubMed  Google Scholar 

  53. Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey TJ, Zentella A, Albert JD, Shires GT, Cerami A: Shock and tissue injury induced by recombinant human cachectin. Science 234: 470–474, 1986

    PubMed  Google Scholar 

  54. Tredget EE, Yu YM, Zhong S, Burini R, Okusawa S, Gelfand JA, Dinarello CA, Young VR, Burke JF: Role of interleukin-1 and tumor necrosis factor of energy metabolism in rabbits. Am J Physiol 255: E760-E768, 1988

    PubMed  Google Scholar 

  55. Grunfeld C, Verdier JA, Neese R, Moser AH, Feingold KR: Mechanisms by which tumor necrosis factor stimulates hepatic fatty acid synthesisin vivo. J Lipid Res 29: 1327–1335, 1988

    PubMed  Google Scholar 

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López-Soriano, J., Argilés, J.M. & López-Soriano, F.J. Metabolic effects of tumour necrosis factor-α on rat brown adipose tissue. Mol Cell Biochem 143, 113–118 (1995). https://doi.org/10.1007/BF01816944

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