title: 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.
  
  
  RESULTS
  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
  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.
authors: Institute of Research and Biotechnology of Strasbourg, Centre national de la recherche scientifique, UMR7242, University of Strasbourg, Medalis/Labex, Drug Discovery Center, Illkirch, France.
authors: Cécilia
authors: C
authors: Szatkowski
authors: Judith
authors: J
authors: Vallet
authors: Mojdeh
authors: M
authors: Dormishian
authors: Nadia
authors: N
authors: Messaddeq
authors: Phillippe
authors: P
authors: Valet
authors: Mounia
authors: M
authors: Boulberdaa
authors: Daniel
authors: D
authors: Metzger
authors: Pierre
authors: P
authors: Chambon
authors: Canan G
authors: CG
authors: Nebigil
mesh_terms: D041721:3T3-L1 Cells; D050153:Abdominal Fat / Q000473:pathology; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology*; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C525015:PKR1 protein, mouse; D043562:Receptors, G-Protein-Coupled