title: JAZF1 regulates visfatin expression in adipocytes via PPARα and PPARβ/δ signaling.
abstract: OBJECTIVE
  Current whole genome-wide association study has identified the association of JAZF1 with type 2 diabetes; its close relation with glucose and lipid metabolism has also been revealed. However, to date, JAZF1 remains a relatively new gene with unknown function.
  
  
  METHODS
  We constructed JAZF1 overexpression vector and synthesized JAZF1 siRNA, then transfected them into 3T3-L1 adipocytes, investigated the relationship between the regulations of JAZF1, visfatin, and other adipokines, researched the specific function of JAZF1 in glucose and lipid metabolism.
  
  
  RESULTS
  This study found that the expression of JAZF1 was gradually but significantly upregulated during the induced differentiation of 3T3-L1 preadipocytes, and that the trend of its expression was consistent with that of visfatin. Further studies indicated that JAZF1 promoted the expressions of visfatin, PPARα, and PPARβ/δ in adipocytes but simultaneously inhibited the expressions of TAK1 and PPARγ. Luciferase reporter assay revealed that JAZF1 activated the transcription of visfatin, but ChIP assay results indicated that JAZF1 did not directly bind to visfatin PPRE. Our results also showed that the JAZF1 overexpression-increased visfatin expression was abolished by the addition of PPARα antagonist GW 6471 and PPARβ/δ antagonist GSK 3787 respectively. And these results were further confirmed by the experiment with PPARα and PPARβ/δ siRNAs. Meanwhile, we also found that JAZF1 inhibited the lipid accumulation during the differentiation of 3T3-L1 into mature adipocyte.
  
  
  CONCLUSIONS
  Our results indicate that JAZF1 might firstly upregulated the expression of PPARα and PPARβ/δ, which in turn activated the transcription of visfatin. JAZF1 plays an important role in lipid metabolism and may thus provide a potential tool for the treatment of obesity and lipid metabolism disorders among other diseases.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; P. R. China; Department of critical care medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Guang-feng
authors.initials: GF
authors.lastname: Ming
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; P. R. China.
authors.forename: Ji-ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of critical care medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Yu-hang
authors.initials: YH
authors.lastname: Ai
authors.affiliation: Department of critical care medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Dao-miao
authors.initials: DM
authors.lastname: Xu
authors.affiliation: Department of critical care medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Ma
authors.affiliation: Department of critical care medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Hui-xia
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; P. R. China.
authors.forename: Hong-hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; P. R. China. Electronic address: liuzhaoqian63@126.com.
authors.forename: Zhao-qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D056970:Co-Repressor Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005453:Fluorescence; D050356:Lipid Metabolism; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C558308:JAZF1 protein, mouse; D009687:Nuclear Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D054409:Nicotinamide Phosphoribosyltransferase
keywords: 3T3-L1; Adipocytes; JAZF1; PPAR; TAK1; Visfatin