Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling.
Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity-associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component beta-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1alpha, GSK-3beta, and Axin, components of the destruction complex targeting beta-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells.
Ahn
Jiyun
J
Food Function Research Center, Korea Food Research Institute, Gyeonggi 463-746, Korea.
Lee
Hyunjung
H
Kim
Suna
S
Ha
Taeyoul
T
D041721:3T3-L1 Cells; D021581:Active Transport, Cell Nucleus; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D060466:Axin Protein; D048128:Casein Kinase Ialpha / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D051157:Frizzled Receptors / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D051379:Mice; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D019440:Anti-Obesity Agents; D060466:Axin Protein; C530105:Ccnd1 protein, mouse; C495268:Ctnnb1 protein, rat; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051157:Frizzled Receptors; C489743:Fzd2 protein, mouse; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; C555484:Lrp5 protein, rat; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D051176:beta Catenin; D019938:Cyclin D1; D048128:Casein Kinase Ialpha; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin