Dataset Information

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

ABSTRACT:

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-2 regulates food intake and energy metabolism via central mechanisms (PKR2). The peripheral effect of prokineticin-2 on adipocytes/preadipocytes has not been studied yet.

Methodology/principal findings

Since adipocytes and preadipocytes express mainly prokineticin receptor-1 (PKR1), here, we explored the role of PKR1 in adipose tissue expansion, generating PKR1-null (PKR1(-/-)) and adipocyte-specific (PKR1(ad-/-)) mutant mice, and using murine and human preadipocyte cell lines. Both PKR1(-/-) and PKR1(ad-/-) had excessive abdominal adipose tissue, but only PKR1(-/-) mice showed severe obesity and diabetes-like syndrome. PKR1(ad-/-)) mice had increased proliferating preadipocytes and newly formed adipocyte levels, leading to expansion of adipose tissue. Using PKR1-knockdown in 3T3-L1 preadipocytes, we show that PKR1 directly inhibits preadipocyte proliferation and differentiation. These PKR1 cell autonomous actions appear targeted at preadipocyte cell cycle regulatory pathways, through reducing cyclin D, E, cdk2, c-Myc levels.

Conclusions/significance

These results suggest PKR1 to be a crucial player in the preadipocyte proliferation and differentiation. Our data should facilitate studies of both the pathogenesis and therapy of obesity in humans.

SUBMITTER: Szatkowski C

PROVIDER: S-EPMC3852222 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Szatkowski Cécilia C Vallet Judith J Dormishian Mojdeh M Messaddeq Nadia N Valet Phillippe P Boulberdaa Mounia M Metzger Daniel D Chambon Pierre P Nebigil Canan G CG

PloS one 20131204 12

<h4>Background</h4>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-2 regulates food intake and energy metabolism via central mechanisms (PKR2). The peripheral effect of prokineticin-2 on adipocytes/preadip ...[more]

PMID: 24324673

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Dataset Information

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

Background

Methodology/principal findings

Conclusions/significance

Publications

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

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