The balance of concentration between Prokineticin 2β and Prokineticin 2 modulates the food intake by STAT3 signaling.

The secreted bioactive peptide prokineticin 2 (PK2) is a potent adipokine and its central and peripheral administration reduces food intake in rodents. The gene has two splice variants, PK2 and PK2L (PK2 long form), which is cleaved into an active peptide, PK2β, that preferentially binds prokineticin receptor 1 (PKR1). We investigated the role of PK2β in the regulation of food intake. We demonstrated that intraperitoneal injection of PK2β, in contrast to PK2, did not reduce food intake in mice. Exposure of hypotalamic explants to PK2, but not PK2β, induced phosphorylation of STAT3 and ERK. We also evidenced that in adipocytes from PKR1 knock-out mice, a model of obesity, there were higher PK2β levels than PK2 inducing a decreased activation of STAT3 and ERK. Our results suggest that variations in PK2 and PK2β levels, due to modulation of gene splicing processes, affect food intake in mice.