title: Trans10, cis12 conjugated linoleic acid inhibits 3T3-L1 adipocyte adipogenesis by elevating β-catenin levels.
abstract: BACKGROUND
  Trans-10, cis-12 (t10-c12) CLA treatment reduces lipid accumulation in differentiating mouse and human adipocytes, and decreases fat mass in mice, yet the mechanism of action remains unknown.
  
  
  OBJECTIVE
  This study investigated the effect of the cis-9, trans-11 (c9-t11) and t10-c12 CLA isomers on the Wnt/β-catenin pathway, which has been reported to inhibit adipogenesis by down-regulating PPARγ.
  
  
  RESULTS
  We observed that t10-c12 CLA treatment of 3T3-L1 adipocytes increases the levels of β-catenin and Ser-675 phosphorylated β-catenin due to inhibition of its degradation. These changes in β-catenin were not linked to either the Wnt/β-catenin agonist Wnt10b or other upstream effectors such as SFRP-5. Paradoxically, the presence of higher amounts of β-catenin did not elevate cyclin D1 levels, which is recognized as a critical target gene. Neither of the CLA isomers affected the localization of β-catenin in the cytosol and nucleus as determined by immunofluorescence microscopy. However, subcellular fractionation suggested the level of cytosolic β-catenin was reduced in t10-c12 CLA treated cells. Immunoprecipitation revealed that t10-c12 CLA increased the interaction of β-catenin and PPARγ.
  
  
  CONCLUSIONS
  t10-c12-CLA inhibits adipocyte differentiation by increasing β-catenin stability in 3T3-L1 adipocytes, thus enhancing sequestration of PPARγ in an inactive complex, which prevents progression of adipogenesis.
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Yeganeh
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Canada; Department of Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Carla G
authors.initials: CG
authors.lastname: Taylor
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Poole
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Leslee
authors.initials: L
authors.lastname: Tworek
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Canada; Department of Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada. Electronic address: peterz@sbrc.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Zahradka
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D055550:Protein Stability; D013997:Time Factors; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D051176:beta Catenin; C496197:trans-10,cis-12-conjugated linoleic acid
keywords: Adipocytes; Adipogenesis; Conjugated linoleic acid (CLA); GSK3-β; PPARγ; Wnt; β-Catenin