Neurturin signaling via Glilal cell line-derived Family Receptor a2 (GFR a2) is required for development and target innervation for subsets of parasympathetic and enteric neurons. Knockout of the receptor gene (Gfra2-/-) in mice leads to postnatal growth impairment. Knockout (KO) mice have deficient innervations, impaired function of exocrine and endocrine pancreas.

The aim of this study was to analyse feeding behavior and metabolic performance using an automated monitoring system. Plasma ghrelin and leptin were analyzed by commercial radioimmunoassays.

Food intake and locomotor activity did not differ between genotypes. In KO mice, the duration of individual meals was ~50% longer, meal sizes were reduced by ~40%, and the number of feeding bouts during dark period was increased by ~40% compared to wildtype (WT). The average time between meals during the night phase was shorter (KO 12 ± 1 min, WT 20 ± 2 min, p < 0,05). Plasma ghrelin was increased in both fasted (~+35%) and fed (~+51%) KO mice compared to WT. Feeding reduced ghrelin levels by 45% in the KO mice. In fed mice, leptin levels were reduced (10,2 ± 1,6 ng/ml in WT to 6,1 ± 0,8 ng/ml in KO, p < 0,05).

Our data suggest that elevated ghrelin levels promote the increase in meal frequency, possibly compensating for the lacking food induced satiety in adult KO mice. Ghrelin secretion is mostly of gastric origin and under cholinergic control. In KO mice, this control seems to be overridden due to deficient peripheral cholinergic innervations, suggesting that high ghrelin levels are a superior physiological adaptation mechanism in order to increase food intake as indicated by increased feeding bouts.