Human IL6 enhances leptin action in mice

Diabetologia. 2010 Mar;53(3):525-35. doi: 10.1007/s00125-009-1580-8. Epub 2009 Nov 10.


Aims/hypothesis: Interleukin-6 is an inflammatory cytokine with pleiotropic effects upon nutrient homeostasis. Many reports show that circulating IL6 correlates with obesity and contributes to insulin resistance; however, IL6 can promote energy expenditure that improves glucose homeostasis.

Methods: We investigated nutrient homeostasis in C57BL/6J mice with sustained circulating human IL6 (hIL6) secreted predominantly from brain and lung (hIL6(tg) mice).

Results: The hIL6(tg) mice displayed no features of systemic inflammation and were more insulin-sensitive than wild-type mice. On a high-fat diet, hIL6(tg) mice were lean, had low leptin concentrations, consumed less food and expended more energy than wild-type mice. Like ob/ob mice, the ob/ob (IL6) mice (generated by intercrossing ob/ob and hIL6(tg) mice) were obese and glucose-intolerant. However, low-dose leptin injections increased physical activity and reduced both body weight and food intake in ob/ob (IL6) mice, but was ineffective in ob/ob mice. Leptin increased hypothalamic signal transducer and activator of transcription-3 phosphorylation in ob/ob (IL6) mice, whereas ob/ob mice barely responded.

Conclusions/interpretation: Human IL6 enhanced central leptin action in mice, promoting nutrient homeostasis and preventing diet-induced obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Crosses, Genetic
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Inflammation
  • Insulin / metabolism
  • Interleukin-6 / metabolism*
  • Leptin / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Mice, Transgenic
  • Obesity / metabolism*
  • Obesity / pathology


  • Insulin
  • Interleukin-6
  • Leptin
  • Glucose