, Volume 53, Issue 3, pp 399–402

IL6 as a mediator of insulin resistance: fat or fiction?



IL6 Insulin sensitivity Leptin Obesity 



AMP-activated protein kinase


Central nervous system


  1. 1.
    Bastard JP, Jardel C, Bruckert E et al (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 85:3338–3342CrossRefPubMedGoogle Scholar
  2. 2.
    Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley RE (2001) Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res 9:414–417CrossRefPubMedGoogle Scholar
  3. 3.
    Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119PubMedGoogle Scholar
  4. 4.
    Lazar MA (2005) How obesity causes diabetes: not a tall tale. Science 307:373–375CrossRefPubMedGoogle Scholar
  5. 5.
    Mohamed-Ali V, Goodrick S, Rawesh A et al (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 82:4196–4200CrossRefPubMedGoogle Scholar
  6. 6.
    Senn JJ, Klover PJ, Nowak IA, Mooney RA (2002) Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 51:3391–3399CrossRefPubMedGoogle Scholar
  7. 7.
    Lagathu C, Bastard JP, Auclair M, Maachi M, Capeau J, Caron M (2003) Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem Biophys Res Commun 311:372–379CrossRefPubMedGoogle Scholar
  8. 8.
    Rotter V, Nagaev I, Smith U (2003) Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 278:45777–45784CrossRefPubMedGoogle Scholar
  9. 9.
    Trujillo ME, Sullivan S, Harten I, Schneider SH, Greenberg AS, Fried SK (2004) Interleukin-6 regulates human adipose tissue lipid metabolism and leptin production in vitro. J Clin Endocrinol Metab 89:5577–5582CrossRefPubMedGoogle Scholar
  10. 10.
    Franckhauser S, Elias I, Rotter Sopasakis V et al (2008) Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice. Diabetologia 51:1306–1316CrossRefPubMedGoogle Scholar
  11. 11.
    Klover PJ, Zimmers TA, Koniaris LG, Mooney RA (2003) Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52:2784–2789CrossRefPubMedGoogle Scholar
  12. 12.
    Kim HJ, Higashimori T, Park SY et al (2004) Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53:1060–1067CrossRefPubMedGoogle Scholar
  13. 13.
    Klover PJ, Clementi AH, Mooney RA (2005) Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology 146:3417–3427CrossRefPubMedGoogle Scholar
  14. 14.
    Febbraio MA, Hiscock N, Sacchetti M, Fischer CP, Pedersen BK (2004) Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 53:1643–1648CrossRefPubMedGoogle Scholar
  15. 15.
    Hiscock N, Chan MH, Bisucci T, Darby IA, Febbraio MA (2004) Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. FASEB J 18:992–994PubMedGoogle Scholar
  16. 16.
    Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund Pedersen B (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529:237–242CrossRefPubMedGoogle Scholar
  17. 17.
    Wojtaszewski JF, Richter EA (2006) Effects of acute exercise and training on insulin action and sensitivity: focus on molecular mechanisms in muscle. Essays Biochem 42:31–46CrossRefPubMedGoogle Scholar
  18. 18.
    Xing Z, Gauldie J, Cox G et al (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101:311–320CrossRefPubMedGoogle Scholar
  19. 19.
    Wallenius V, Wallenius K, Ahren B et al (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79CrossRefPubMedGoogle Scholar
  20. 20.
    Carey AL, Steinberg GR, Macaulay SL et al (2006) Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55:2688–2697CrossRefPubMedGoogle Scholar
  21. 21.
    Sadagurski MNL, Farhang J, D’Aquino K, Copps K, White MF (2009) Human IL6 enhances leptin action in mice. Diabetologia DOI:10.1007/s00125-009-1580-8
  22. 22.
    Wallenius K, Wallenius V, Sunter D, Dickson SL, Jansson JO (2002) Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 293:560–565CrossRefPubMedGoogle Scholar
  23. 23.
    Tsigos C, Papanicolaou DA, Defensor R, Mitsiadis CS, Kyrou I, Chrousos GP (1997) Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 66:54–62CrossRefPubMedGoogle Scholar
  24. 24.
    Rothwell NJ, Busbridge NJ, Lefeuvre RA, Hardwick AJ, Gauldie J, Hopkins SJ (1991) Interleukin-6 is a centrally acting endogenous pyrogen in the rat. Can J Physiol Pharmacol 69:1465–1469PubMedGoogle Scholar
  25. 25.
    Li G, Klein RL, Matheny M, King MA, Meyer EM, Scarpace PJ (2002) Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats. Neuroscience 115:879–889CrossRefPubMedGoogle Scholar
  26. 26.
    Minokoshi Y, Kim YB, Peroni OD et al (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343CrossRefPubMedGoogle Scholar
  27. 27.
    Steinberg GR, Rush JW, Dyck DJ (2003) AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment. Am J Physiol Endocrinol Metab 284:E648–E654PubMedGoogle Scholar
  28. 28.
    Watt MJ, Dzamko N, Thomas WG et al (2006) CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 12:541–548CrossRefPubMedGoogle Scholar
  29. 29.
    Bruce CR, Dyck DJ (2004) Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha. Am J Physiol Endocrinol Metab 287:E616–E621CrossRefPubMedGoogle Scholar
  30. 30.
    Luheshi G, Miller AJ, Brouwer S, Dascombe MJ, Rothwell NJ, Hopkins SJ (1996) Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat. Am J Physiol 270:E91–E95PubMedGoogle Scholar
  31. 31.
    Febbraio MA (2007) gp130 receptor ligands as potential therapeutic targets for obesity. J Clin Invest 117:841–849CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Cellular and Molecular Metabolism LaboratoryBaker IDI Heart & Diabetes InstituteMelbourneAustralia

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