GIP receptor agonism suppresses inflammation-induced aversion and food intake via distinct circuits
Glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone, and pharmacologic modulation of central GIP receptors (GIPR) improves energy homeostasis. Recent reports have demonstrated that GIPR agonism is also anti-aversive. However, the mechanisms by which GIPR signaling impact food intake and aversion are incompletely understood. Here, we show that GIPR agonism abrogatesthe aversive and enhances the anorexigenic effects of the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). Aversion-encoding parabrachial calcitonin-gene related peptide (CGRP) neurons were required for IL-1{beta}-induced conditioned taste avoidance (CTA) but not anorexia. Moreover, systemic IL-1{beta} increased in vivo CGRP neural activity, and this was significantly attenuated by co-administration of a GIPR agonist. By contrast, GIPR in the dorsal vagal complex were required for the acute anorectic effect of GIPR agonism but not its anti-aversive effect. Taken together, our data suggest that GIPR agonism reduces food intake and prevents aversion via distinct circuits, and that GIPR agonism may represent an effective approach to alleviate inflammation-induced aversion.