Short communicationImpaired suppression of feeding by the gut hormone xenin in type I interleukin-1 receptor-deficient mice

- Intraperitoneal injection of xenin increased IL-1β mRNA levels in the hypothalamus.
- Injection of xenin reduced food intake in wild-type mice.
- Xenin treatment failed to reduce food intake in pre-obese IL-1RI KO mice.

Xenin is a gut hormone that reduces food intake partly by acting through the hypothalamus. However, the mechanism of hypothalamic xenin action is not fully understood. To identify xenin-regulated genes in the hypothalamus, we compared expression levels of metabolism-related genes in the hypothalamus between saline-treated control and xenin-treated mice. Intraperitoneal injection of xenin caused a significant increase in hypothalamic interleukin 1 beta (IL-1β) mRNA levels without causing a significant change in hypothalamic IL-1α mRNA levels. To further examine the possible contribution of IL-1 signaling to xenin's anorexigenic action, the effect of intraperitoneal injection of xenin on food intake was compared between wild-type and type I IL-1 receptor (IL-1RI)-deficient mice. Intraperitoneal administration of xenin (7.5 μg/g b.w.) caused a significant reduction of food intake in wild-type mice, while it failed to reduce food intake in pre-obese IL-1RI-deficient mice. These findings support the role of hypothalamic IL-1β-IL-1RI signaling in the mediation of the anorexigenic effect of xenin.