Abstract 15414: Prokineticin Receptor 1 as a Novel Suppressor of Preadipocyte Proliferation and Differentiation to Control Obesity
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 hormon that activate two G protein-coupled receptors: PKR1 and PKR2. Prokineticin-2 regulates food intake and energy metabolism via central mechanisms (PKR2). The peripheral effect of prokineticin-2 on adipocytes has not been studied yet. Since adipocytes and preadipocytes express mainly prokineticin receptor-1 (PKR1), here, we explored the role of PKR1 in adipocyte/preadipocyte functions, generating PKR1-null (PKR1-/-) and adipocyte-specific (PKR1ad-/-) mutant mice, and using murine and human preadipocyte cell lines. Both PKR1-/- and PKR1ad-/- had excessive adipose tissue, but only PKR1-/- mice showed severe obesity and diabetes-like syndrome. Adipocyte-specific loss of PKR1 elevated proliferation of preadipocytes, promoted the formation of new adipocytes, and produced expansion of adipose tissue. Using PKR1-knockdown in 3T3-L1 preadipocytes, we show that PKR1 directly inhibits preadipocyte proliferation and differentiation. Hence, autocrine and paracrine PKR1 functions regulate preadipocyte proliferation, and conversion of preadipocytes to adipocytes. This opens up the possible pharmacological use of PKR1 agonists for the clinical treatment of obesity.
- © 2013 by American Heart Association, Inc.