title: GPR39 activates proliferation and differentiation of porcine intramuscular preadipocytes through targeting the PI3K/AKT cell signaling pathway.
abstract: BACKGROUND
  The orphan G protein-coupled receptor (GPR) 39 was originally identified as the receptor of obestatin. In this study, the effects and mechanisms of GPR39 on cell proliferation and differentiation were investigated in cultured porcine intramuscular preadipocytes.
  
  
  METHODS
  Morphology of preadipocytes and accumulated lipid droplets within cells were identified by an inverted microscope. After transfected with constructed pCMV-GPR39 plasmid, cell proliferation was measured by using methyl thiazolyl tetrazolium method, mRNA expression of GPR39, CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), Caspase-9 and adipocyte determination and differentiation factor-1 (ADD1) was determined by RNA preparation and reverse transcription polymerase chain reaction, protein expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1, phosphorylated glycogen synthase kinase 3 (pGSK3), total Akt and phosphorylated Akt (pAkt) was analyzed by Western blot.
  
  
  RESULTS
  It found that GPR39 mRNA and protein were expressed in porcine intramuscular preadipocytes and its expression was significantly up-regulated after treatment with Zn(2+) whose function is found to be mediated by GPR39. Furthermore, over-expression of GPR39 further promoted the optical density value of cells, enhanced mRNA expression of PPARγ, C/EBPα and ADD1, and inhibited mRNA expression of Caspase-9. Protein expression of pGSK3 and pAkt was also increased by GPR39 stimulation. In addition, GPR39-induced proliferation and differentiation of porcine intramuscular preadipocytes was partially blocked by the Akt inhibitor (PDTC) and the PI3K inhibitor (LY294002).
  
  
  CONCLUSIONS
  It indicated that GPR39 was a transducer of Zn(2+), and enhanced proliferation and differentiation of porcine intramuscular preadipocytes through activation of the PI3K/Akt signaling pathway.
authors.affiliation: a College of Yingdong Agricultural Science and Engineering, Shaoguan University , Shaoguan , P.R. China .
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Dong
authors.affiliation: a College of Yingdong Agricultural Science and Engineering, Shaoguan University , Shaoguan , P.R. China .
authors.forename: Shengqiu
authors.initials: S
authors.lastname: Tang
authors.affiliation: b Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Hubei Academy of Agricultural Science , Wuhan , P.R. China .
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: c College of Animal Science, Yangtze Univeisity , Jingzhou , P.R. China , and.
authors.forename: Weihua
authors.initials: W
authors.lastname: Gao
authors.affiliation: d College of Yingdong Life Science, Shaoguan University , Shaoguan , P.R. China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Chen
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis / Q000235:genetics; D053453:Caspase 9 / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D066292:Lipid Droplets / Q000187:drug effects; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D013552:Swine; D015032:Zinc / Q000494:pharmacology*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D051780:Sterol Regulatory Element Binding Protein 1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053453:Caspase 9; D015032:Zinc
keywords: Akt; GPR39; PI3K; differentiation; inhibitor; preadipocyte; proliferation