Published in:
Open Access 01-03-2010 | Article
Human IL6 enhances leptin action in mice
Published in: Diabetologia | Issue 3/2010
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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.