Central Interleukin-1 (IL1) Signaling is Required For Pharmacological, but not Physiological, Effects of Leptin on Energy Balance

Hypothalamic IL1 is suggested to be a critical mediator of the central effects of the adipocyte hormone leptin on energy balance. We hypothesized that IL1 receptor signaling is required for exogenously administered leptin to cause anorexia and weight loss, but not for physiological effects of endogenous leptin signaling on energy balance. To test this hypothesis, we investigated whether chronic hypothalamic over-expression of an IL1 receptor antagonist (AdV-IL1ra) alters food intake and weight gain in normal rats. Our findings demonstrate that impaired IL1 signaling in the CNS did not cause excess weight gain over a period of 11 days (AdV-IL1ra +38.1+/-4.1 g vs. VEH +42.2+/-5.6g; p=0.6) and caused a slightly reduced daily food intake (AdV-IL1ra 29.0+/-1.1 g/day vs. VEH 33.0+/-1.6 g/day; p