Effects of prolactin-releasing peptide on food intake and metabolism

Abstract

Food intake is controlled by signals from the brainstem that mediate signals from the gut. Prolactin-releasing peptide (PrRP) neurons are localized in the brainstem. In the present study, we investigated whether food intake activates PrRP neurons. We examined expression of phospho-CREB in PrRP neurons after food intake. The percentage of phospho-CREB-positive PrRP neurons in the nucleus of tractus solitarii was increased by food intake, suggesting that food intake activates PrRP neurons in the nucleus tractus solitarii. To further study the role of endogenous PrRP in food intake, we generated PrRP-deficient mice. PrRP-deficient mice developed late onset obestity associated with metabolic disorders due to hyperphagia but not to energy expenditure, and showed an attenuated response to the peripheral satiety signal, cholecystokinin. Blockade of endogenous PrRP signaling by a central injection of monoclonal anti-PrRP neutralizing antibodies increased food intake, reflecting an increase in meal size. Furthermore, we demonstrated that leptin-induced reduction in food intake and body weight was impaired in PrRP-deficient mice. All these data suggest that PrRP relays satiety signals within the brain and that disturbance of this system can result in obesity and associated metabolic disorders. [J Physiol Sci. 2008;58 Suppl:S106]