Role of IL-6 in Energy Expenditure

Interleukin 6 (IL-6) is produced by adipose tissue under non-inflammatory conditions1,2 and has been shown to be mildly elevated in obesity. Similar to leptin, serum IL-6 levels correlate with Body Mass Index (BMI).1-3 IL-6 knockout (IL-6 K/O) mice have been shown to develop mature-onset obesity, weighing approximately 20% more than wild type (WT) at 9 months, with primarily an increase in subcutaneous fat mass. Mature IL-6 K/O mice exhibit abnormal blood lipid and carbohydrate metabolism, have increased plasma leptin levels, and do not respond to leptin treatment. In contrast, mature WT mice show a significant decrease in both body weight and food intake in response to leptin treatment.4

IL-6 and its receptors are found in the hypothalamic nuclei, which regulate metabolism.5,6 IL-6 activates the hypothalamic-pituitary-adrenal (HPA) system in conscious, freely-moving rats, thus suggesting that it may mediate an interaction between the neuroendocrine and immune systems.7

A low dose regimen of intra-cerebroventricular IL-6 replacement in IL-6 K/O mice has resulted in a significant decrease in body weight and fat mass, and an increase in oxygen consumption without inducing an acute-phase reaction. This response was not observed in the WT or intraperitoneally-treated IL-6 K/O mice. This result suggests that IL-6 acts centrally, not peripherally, to increase energy expenditure.4

References

  1. Mohamed, A.V. et al. (1997) J. Clin. Endocrinol. Metab. 82:4196.
  2. Fried, S.K. et al. (1998) J. Clin. Endocrinol. Metab. 83:847.
  3. Vgontzas, A.N. et al. (2000) J. Clin. Endocrinol. Metab. 85:1151.
  4. Wallenius, V. (2002) Nature Med. 8:75.
  5. Schobitz, B. et al. (1993) Eur. J. Neurosci. 5:1426.
  6. Shizuya, K. et al. (1998) Life Sci. 62:2315.
  7. Naitoh, Y. et al. (1988) Biochem. Biophys. Res. Commun. 155:1459.