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

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Fig. 1

Abbreviations

AMPK:

AMP-activated protein kinase

CNS:

Central nervous system

References

  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 85:3338–3342

    Article  CAS  PubMed  Google Scholar 

  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 9:414–417

    Article  CAS  PubMed  Google Scholar 

  3. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119

    CAS  PubMed  Google Scholar 

  4. Lazar MA (2005) How obesity causes diabetes: not a tall tale. Science 307:373–375

    Article  CAS  PubMed  Google Scholar 

  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 82:4196–4200

    Article  CAS  PubMed  Google Scholar 

  6. Senn JJ, Klover PJ, Nowak IA, Mooney RA (2002) Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 51:3391–3399

    Article  CAS  PubMed  Google Scholar 

  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 311:372–379

    Article  CAS  PubMed  Google Scholar 

  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 278:45777–45784

    Article  CAS  PubMed  Google Scholar 

  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 89:5577–5582

    Article  CAS  PubMed  Google Scholar 

  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 51:1306–1316

    Article  CAS  PubMed  Google Scholar 

  11. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA (2003) Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52:2784–2789

    Article  CAS  PubMed  Google Scholar 

  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 53:1060–1067

    Article  CAS  PubMed  Google Scholar 

  13. Klover PJ, Clementi AH, Mooney RA (2005) Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology 146:3417–3427

    Article  CAS  PubMed  Google Scholar 

  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 53:1643–1648

    Article  CAS  PubMed  Google Scholar 

  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 18:992–994

    CAS  PubMed  Google Scholar 

  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 529:237–242

    Article  CAS  PubMed  Google Scholar 

  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 42:31–46

    Article  CAS  PubMed  Google Scholar 

  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 101:311–320

    Article  CAS  PubMed  Google Scholar 

  19. Wallenius V, Wallenius K, Ahren B et al (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79

    Article  CAS  PubMed  Google Scholar 

  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 55:2688–2697

    Article  CAS  PubMed  Google Scholar 

  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. Wallenius K, Wallenius V, Sunter D, Dickson SL, Jansson JO (2002) Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 293:560–565

    Article  CAS  PubMed  Google Scholar 

  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 66:54–62

    Article  CAS  PubMed  Google Scholar 

  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 69:1465–1469

    CAS  PubMed  Google Scholar 

  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 115:879–889

    Article  CAS  PubMed  Google Scholar 

  26. Minokoshi Y, Kim YB, Peroni OD et al (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343

    Article  CAS  PubMed  Google Scholar 

  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–E654

    CAS  PubMed  Google Scholar 

  28. Watt MJ, Dzamko N, Thomas WG et al (2006) CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 12:541–548

    Article  CAS  PubMed  Google Scholar 

  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–E621

    Article  CAS  PubMed  Google Scholar 

  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–E95

    CAS  PubMed  Google Scholar 

  31. Febbraio MA (2007) gp130 receptor ligands as potential therapeutic targets for obesity. J Clin Invest 117:841–849

    Article  CAS  PubMed  Google Scholar 

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Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

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Authors and Affiliations

  1. Cellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, 3008, VIC, Australia

    T. L. Allen & M. A. Febbraio

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  1. T. L. Allen
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  2. M. A. Febbraio
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Correspondence to M. A. Febbraio.

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Allen, T.L., Febbraio, M.A. IL6 as a mediator of insulin resistance: fat or fiction?. Diabetologia 53, 399–402 (2010). https://doi.org/10.1007/s00125-009-1627-x

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