title: Prolyl isomerase Pin1 regulates mouse embryonic fibroblast differentiation into adipose cells.
abstract: BACKGROUND
  A peptidyl prolyl cis/trans isomerase, Pin1, regulates insulin signal transduction. Pin1 reduces responses to insulin stimulation by binding CRTC2 (CREB-regulated transcriptional co-activator 2) and PPARγ (peroxisome prolifereator- activated receptor γ), but conversely enhances insulin signaling by binding IRS-1 (insulin receptor substrate-1), Akt kinase, and Smad3. Therefore, it is still unclear whether Pin1 inhibits or enhances adipose cell differentiation.
  
  
  RESULTS
  Pin1(-/-) and wild-type mice were fed with high fat diets and adipose tissue weight was measured. Compared to wild-type mice, Pin1(-/-) mice had lower adipose tissue weight, while the weight of other tissues was similar. Mouse embryo fibroblasts (MEFs), prepared from both groups of mice, were induced to differentiate into adipose cells by stimulation with insulin. However, the rate of differentiation of MEFs from Pin1(-/-) mice was less than that of MEFs from wild-type mice. The rate of insulin-induced MEF cell differentiation in Pin1(-/-) mice was restored by increasing expression of Pin1. We found that Pin1 binds to phosphoThr172- and phosphoSer271-Pro sites in CREB suppress the activity in COS-7 cells.
  
  
  CONCLUSIONS
  Pin1 enhanced the uptake of triglycerides and the differentiation of MEF cells into adipose cells in response to insulin stimulation. Results of this study suggest that Pin1 down-regulation could be a potential approach in obesity-related dysfunctions, such as high blood pressure, diabetes, non-alcoholic steatohepatitis.
authors.affiliation: Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan. uchidat@biochem.tohoku.ac.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Uchida
authors.forename: Kengo
authors.initials: K
authors.lastname: Furumai
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
authors.forename: Hirotada
authors.initials: H
authors.lastname: Akiyama
authors.forename: Mika
authors.initials: M
authors.lastname: Takezawa
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujimori
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Uchida
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology*; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D048429:Cell Size; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D059305:Diet, High-Fat; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014057:Tomography, X-Ray Computed; D015533:Transcriptional Activation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse