title: Twist 1 regulates the expression of PPARγ during hormone-induced 3T3-L1 preadipocyte differentiation: a possible role in obesity and associated diseases.
abstract: BACKGROUND
  Twist 1 is highly expressed in adipose tissue and has been associated with obesity and related disorders. However, the molecular function of Twist 1 in adipose tissue is unclear. Twist 1 has been implicated in cell lineage determination and differentiation. Therefore, we investigated both the role of Twist 1 in adipocyte precursor mobilization and the relationship of Twist 1 with other molecular determinants of adipocyte differentiation.
  
  
  METHODS
  We examined Twist 1 mRNA and protein expression in subcutaneous adipose tissues from diet-induced obese C57/BL6 mice and Wistar rats and in obese patients undergoing liposuction or adipose transplant surgeries. Twist 1 expression was measured on days 0, 2, 4, 8, and 12 of 3T3-L1 differentiation in vitro. The role of Twist 1 in adipogenesis was explored using retroviral interference of Twist 1 expression. Adipokine secretion was evaluated using a RayBio® Biotin Label-based Adipokine Array.
  
  
  RESULTS
  Twist 1 mRNA and protein levels were reduced in diet-induced obese mice and rats and in obese humans. Twist 1 was upregulated during 3T3-L1 preadipocyte differentiation in vitro, beginning from the fourth day of differentiation induction. Retroviral interference of Twist 1 expression did not significantly impair lipid formation; however, retroviral interference induced PPARγ mRNA and protein expression on day 4 of differentiation induction. Adipokine array analyses revealed increased secretion of CXCR4 (19.55-fold), VEGFR1 (92.13-fold), L-21 R (63.55-fold), and IL-12 R beta 1 (59.66-fold) and decreased secretion of VEGFR3 (0.01-fold), TSLP R (0.071-fold), MIP-1 gamma (0.069-fold), TNF RI/TNFRSF1A (0.09-fold), and MFG-E8 (0.06-fold).
  
  
  CONCLUSIONS
  Twist 1 is a regulator of adipocyte gene expression although it is not likely to regulate differentiation. We identified PPARγ as a potential target of Twist 1 and found variation in the secretion of multiple adipokines, which might indicate a prospective mechanism linking Twist 1 expression with obesity or associated diseases.
authors.forename: Wanshan
authors.initials: W
authors.lastname: Ma
authors.forename: Sumei
authors.initials: S
authors.lastname: Lu
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Ruxing
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Medical Research & Laboratory Diagnostic Center, Jinan Center Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P,R, China. mwsqianyi@163.com.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006728:Hormones / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D017208:Rats, Wistar; D050151:Subcutaneous Fat / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000502:physiology*
chemical_list: D054392:Adipokines; D006728:Hormones; D009687:Nuclear Proteins; D047495:PPAR gamma; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse