The balance of concentration between Prokineticin 2 β 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 pk2 gene has two splice variants, PK2 and PK2L (PK2 long form), which is cleaved into an active peptide, PK2 beta , that preferentially binds prokineticin receptor 1 (PKR1). We investigated the role of PK2 beta in the regulation of food intake. We demonstrated that intraperitoneal injection of PK2 beta , in contrast to PK2, did not reduce food intake in mice. Exposure of hypotalamic explants to PK2, but not PK2 beta , induced phosphorylation of STAT3 and ERK. We also evidenced that in adipocytes from PKR1 knock -out mice, a model of obesity, there were higher PK2 beta levels than PK2 inducing a decreased activation of STAT3 and ERK. Our results suggest that variations in PK2 and PK2 beta levels, due to modulation of pk2 gene splicing processes, affect food intake in mice.