Article

Diabetologia

, Volume 53, Issue 3, pp 525-535

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Human IL6 enhances leptin action in mice

  • M. SadagurskiAffiliated withHoward Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories
  • , L. NorquayAffiliated withHoward Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories
  • , J. FarhangAffiliated withHoward Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories
  • , K. D’AquinoAffiliated withHoward Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories
  • , K. CoppsAffiliated withHoward Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories
  • , M. F. WhiteAffiliated withHoward Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories Email author 

Abstract

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.

Keywords

Diabetes IL6 Insulin resistance Leptin Leptin sensitivity Obesity