| First Author | Yeganeh A | Year | 2016 |
| Journal | Biochim Biophys Acta | Volume | 1861 |
| Issue | 4 | Pages | 363-70 |
| PubMed ID | 26780430 | Mgi Jnum | J:250759 |
| Mgi Id | MGI:6104539 | Doi | 10.1016/j.bbalip.2016.01.004 |
| Citation | Yeganeh A, et al. (2016) Trans10, cis12 conjugated linoleic acid inhibits 3T3-L1 adipocyte adipogenesis by elevating beta-catenin levels. Biochim Biophys Acta 1861(4):363-70 |
| abstractText | 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/beta-catenin pathway, which has been reported to inhibit adipogenesis by down-regulating PPARgamma. RESULTS: We observed that t10-c12 CLA treatment of 3T3-L1 adipocytes increases the levels of beta-catenin and Ser-675 phosphorylated beta-catenin due to inhibition of its degradation. These changes in beta-catenin were not linked to either the Wnt/beta-catenin agonist Wnt10b or other upstream effectors such as SFRP-5. Paradoxically, the presence of higher amounts of beta-catenin did not elevate cyclin D1 levels, which is recognized as a critical target gene. Neither of the CLA isomers affected the localization of beta-catenin in the cytosol and nucleus as determined by immunofluorescence microscopy. However, subcellular fractionation suggested the level of cytosolic beta-catenin was reduced in t10-c12 CLA treated cells. Immunoprecipitation revealed that t10-c12 CLA increased the interaction of beta-catenin and PPARgamma. CONCLUSIONS: t10-c12-CLA inhibits adipocyte differentiation by increasing beta-catenin stability in 3T3-L1 adipocytes, thus enhancing sequestration of PPARgamma in an inactive complex, which prevents progression of adipogenesis. |
