Interleukin-6-deficient mice develop mature-onset obesity (original) (raw)

References

  1. Barsh, G.S., Farooqi, I.S. & O'Rahilly, S. Genetics of body-weight regulation. Nature 404, 644–651 (2000).
    Article CAS Google Scholar
  2. Friedman, J.M. & Halaas, J.L. Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998).
    Article CAS Google Scholar
  3. Robinson, S.W., Dinulescu, D.M. & Cone, R.D. Genetic models of obesity and energy balance in the mouse. Annu. Rev. Genet. 34, 687–745 (2000).
    Article CAS Google Scholar
  4. Kopf, M. et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368, 339–342 (1994).
    Article CAS Google Scholar
  5. Mohamed-Ali, V. et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J. Clin. Endocrinol. Metab. 82, 4196–4200 (1997).
    CAS Google Scholar
  6. Fried, S.K., Bunkin, D.A. & Greenberg, A.S. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: Depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83, 847–850 (1998).
    CAS PubMed Google Scholar
  7. Vgontzas, A.N. et al. Sleep apnea and daytime sleepiness and fatigue: Relation to visceral obesity, insulin resistance, and hypercytokinemia. J. Clin. Endocrinol. Metab. 85, 1151–1158 (2000).
    Article CAS Google Scholar
  8. Flier, J.S. & Foster, D.W. Eating disorders: Obesity, anorexia nervosa, and bulimia nervosa. in Williams textbook of endocrinology (eds. Williams, R.H., Wilson, J.D., Foster, D.W., Kronenberg, H.M. & Larsen, P.R.) 1061–1097 (Saunders, Philadelphia, 1998).
    Google Scholar
  9. Schobitz, B., de Kloet, E.R., Sutanto, W. & Holsboer, F. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Eur. J. Neurosci. 5, 1426–1435 (1993).
    Article CAS Google Scholar
  10. Shizuya, K. et al. The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress. Life Sci. 62, 2315–2320 (1998).
    Article CAS Google Scholar
  11. Aschner, M. Immune and inflammatory responses in the CNS: Modulation by astrocytes. Toxicol. Lett. 102–103, 283–287 (1998).
    Article Google Scholar
  12. Bastard, J.P. et al. 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 (2000).
    CAS PubMed Google Scholar
  13. Greenberg, A.S. et al. Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. Cancer Res. 52, 4113–4116 (1992).
    CAS PubMed Google Scholar
  14. Nonogaki, K. et al. Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology 136, 2143–2149 (1995).
    Article CAS Google Scholar
  15. Tsigos, C. et al. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J. Clin. Endocrinol. Metab. 82, 4167–4170 (1997).
    Article CAS Google Scholar
  16. Chrousos, G.P. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N. Engl. J. Med. 332, 1351–1362 (1995).
    Article CAS Google Scholar
  17. Bjorntorp, P. Body fat distribution, insulin resistance, and metabolic diseases. Nutrition 13, 795–803 (1997).
    Article CAS Google Scholar
  18. Ershler, W.B. & Keller, E.T. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu. Rev. Med. 51, 245–270 (2000).
    Article CAS Google Scholar
  19. Staels, B. et al. Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators. Nature 393, 790–793 (1998).
    Article CAS Google Scholar
  20. McCarty, M.F. Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline. Med. Hypotheses 52, 465–477 (1999).
    Article CAS Google Scholar
  21. Yudkin, J.S., Kumari, M., Humphries, S.E. & Mohamed-Ali, V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148, 209–214 (1999).
    Article Google Scholar
  22. Luheshi, G.N., Gardner, J.D., Rushforth, D.A., Loudon, A.S. & Rothwell, N.J. Leptin actions on food intake and body temperature are mediated by IL-1. Proc. Natl. Acad. Sci. USA 96, 7047–7052 (1999).
    Article CAS Google Scholar
  23. Rothwell, N.J. et al. Interleukin-6 is a centrally acting endogenous pyrogen in the rat. Can. J. Physiol. Pharmacol. 69, 1465–1469 (1991).
    Article CAS Google Scholar
  24. Gloaguen, I. et al. Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. Proc. Natl. Acad. Sci. USA 94, 6456–6461 (1997).
    Article CAS Google Scholar
  25. Lambert, P.D. et al. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin- resistant obesity. Proc. Natl. Acad. Sci. USA 98, 4652–4657 (2001).
    Article CAS Google Scholar
  26. Bray, G.A. & Tartaglia, L.A. Medicinal strategies in the treatment of obesity. Nature 404, 672–677 (2000).
    Article CAS Google Scholar
  27. Sleeman, M.W., Anderson, K.D., Lambert, P.D., Yancopoulos, G.D. & Wiegand, S.J. The ciliary neurotrophic factor and its receptor, CNTFRα. Pharm. Acta Helv. 74, 265–272 (2000).
    Article CAS Google Scholar
  28. Espat, N.J. et al. Ciliary neurotrophic factor is catabolic and shares with IL-6 the capacity to induce an acute phase response. Am. J. Physiol. 271, R185–190 (1996).
    CAS PubMed Google Scholar
  29. Bjorbaek, C. et al. Activation of SOCS-3 messenger ribonucleic acid in the hypothalamus by ciliary neurotrophic factor. Endocrinology 140, 2035–2043 (1999).
    Article CAS Google Scholar
  30. Xing, Z. et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J. Clin. Invest 101, 311–320 (1998).
    Article CAS Google Scholar
  31. Pedersen, B.K., Steensberg, A. & Schjerling, P. Muscle-derived interleukin-6: possible biological effects. J. Physiol. 536, 329–337 (2001).
    Article CAS Google Scholar
  32. Sjogren, K. et al. Liver-derived IGF-I is of importance for normal carbohydrate and lipid metabolism. Diabetes 50, 1539–1545 (2001).
    Article CAS Google Scholar
  33. Ahren, B., Mansson, S., Gingerich, R.L. & Havel, P.J. Regulation of plasma leptin in mice: Influence of age, high-fat diet, and fasting. Am. J. Physiol. 273, R113–120 (1997).
    Google Scholar
  34. Verdrengh, M. & Tarkowski, A. Role of macrophages in Staphylococcus aureus-induced arthritis and sepsis. Arthritis Rheum. 43, 2276–2282 (2000).
    Article CAS Google Scholar
  35. Liao, W., Rudling, M. & Angelin, B. Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression. Biochem. J. 313, 873–878 (1996).
    Article CAS Google Scholar
  36. Dickson, S.L., Leng, G., Dyball, R.E. & Smith, R.G. Central actions of peptide and non-peptide growth hormone secretagogues in the rat. Neuroendocrinology 61, 36–43 (1995).
    Article CAS Google Scholar

Download references