Human IL6 enhances leptin action in mice.
OBJECTIVE
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
Human IL6 enhanced central leptin action in mice, promoting nutrient homeostasis and preventing diet-induced obesity.
Sadagurski
M
M
Howard Hughes Medical Institute, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Rm 4210, 300 Longwood Avenue, Boston, MA 02115, USA.
Norquay
L
L
Farhang
J
J
D'Aquino
K
K
Copps
K
K
White
M F
MF
D000821:Animal Feed; D000818:Animals; D003433:Crosses, Genetic; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism* / Q000473:pathology
D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D005947:Glucose