Article Dans Une Revue PLoS ONE Année : 2013

Prokineticin Receptor 1 as a Novel Suppressor of Preadipocyte Proliferation and Differentiation to Control Obesity

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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 (PKR1ad−/−) mutant mice, and using murine and human preadipocyte cell lines. Both PKR1−/− and PKR1ad−/− had excessive abdominal adipose tissue, but only PKR1−/− mice showed severe obesity and diabetes-like syndrome. PKR1ad−/−) 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
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hal-02391049 , version 1 (04-02-2025)

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Cécilia Szatkowski, Judith Vallet, Mojdeh Dormishian, Nadia Messaddeq, Phillippe Valet, et al.. Prokineticin Receptor 1 as a Novel Suppressor of Preadipocyte Proliferation and Differentiation to Control Obesity. PLoS ONE, 2013, 8 (12), pp.e81175. ⟨10.1371/journal.pone.0081175⟩. ⟨hal-02391049⟩
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