Prokineticin receptor 1 as a novel suppressor of preadipocyte proliferation and differentiation to control obesity.

Background: Adipocyte renewal from preadipocytes occurs throughout the lifetime and contributes to obesity. To date, little is known about the mechanisms that control preadipocyte proliferation and differentiation. Prokineticin-2 is an angiogenic and anorexigenic hormone that activate two G protein-coupled receptors (GPCRs): PKR1 and PKR2.

Prokineticin receptor-1 is a new regulator of endothelial insulin uptake and capillary formation to control insulin sensitivity and cardiovascular and kidney functions.

Background: Reciprocal relationships between endothelial dysfunction and insulin resistance result in a vicious cycle of cardiovascular, renal, and metabolic disorders. The mechanisms underlying these impairments are unclear. The peptide hormones prokineticins exert their angiogenic function via prokineticin receptor-1 (PKR1).

Genetic inactivation of prokineticin receptor-1 leads to heart and kidney disorders.

Objective: Prokineticins are potent angiogenic hormones that use 2 receptors, prokineticin receptor-1 (PKR1) and PKR2, with important therapeutic use in anticancer therapy. Observations of cardiac and renal toxicity in cancer patients treated with antiangiogenic compounds led us to explore how PKR1 signaling functioned in heart and kidney in vivo.

Methods And Results: We generated mice with a conditional disruption of the PKR1 gene.