Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19

Abstract

Adropin, a recently described peptide hormone produced in the brain and liver, has been reported to have physiologically relevant actions on glucose homeostasis and lipogenesis, and to exert significant effect on endothelial function. We describe a central nervous system action of adropin to inhibit water drinking and identify a potential adropin receptor, the orphan G protein-coupled receptor, GPR19. Reduction in GPR19 mRNA levels in medial basal hypothalamus of male rats resulted in the loss of the inhibitory effect of adropin on water deprivation-induced thirst. The identification of a novel brain action of adropin and a candidate receptor for the peptide should extend and accelerate the study of the potential therapeutic value of adropin or its mimetics for the treatment of metabolic disorders.

Keywords: G protein-coupled receptor; adropin; hypothalamus; thirst.

Fig. 1.

The effect of intracerebroventricular administration of adropin on light-entrained water drinking (A) and food intake (B) in male rats. *P < 0.05, **P < 0.01 vs. vehicle controls (ANOVA and Scheffé's multiple comparisons).

Fig. 2.

Central administration of adropin 10 min prior to the return of water bottles to the cages inhibited water drinking in response to overnight water deprivation in male rats. *P < 0.05 vs. saline control (ANOVA and Scheffé's multiple comparisons).

Fig. 3.

siRNA induced reduction in GPR19 mRNA levels in medial basal hypothalamus blocked the inhibitory action of 3.0-nm adropin, given intracerebroventricular 10 min before return of water bottles to the cages, on overnight water deprivation-induced drinking in male rats. *P < 0.05, **P < 0.01 vs. EGFP siRNA-retreated controls.

Fig. 4.

Central administration of 10 or 3.0 nm of adropin failed to significantly elevate mean arterial pressure (MAP) in conscious, unrestrained male rats. Data are presented as change from preinjection baselines in terms of area under the curve, with MAP recorded every minute for 30 min postinjection.