Vitisin A inhibits adipocyte differentiation through cell cycle arrest in 3T3-L1 cells.
Inhibition of adipocyte differentiation is one approach among the anti-obesity strategies. This study demonstrates that vitisin A, a resveratrol tetramer, inhibits adipocyte differentiation most effectively of 18 stilbenes tested. Fat accumulation and PPARgamma expression were decreased by vitisin A in a dose-dependent manner. Vitisin A significantly inhibited preadipocyte proliferation and consequent differentiation within the first 2 days of treatment, indicating that the anti-adipogenic effect of vitisin A was derived from anti-proliferation. Based on cell cycle analysis, vitisin A blocked the cell cycle at the G1-S phase transition, causing cells to remain in the preadipocyte state. Vitisin A increased p21 expression, while the Rb phosphorylation level was reduced. Therefore, vitisin A seems to induce G1 arrest through p21- and consequent Rb-dependent suppression of transcription. On the other hand, ERK and Akt signaling pathways were not involved in the anti-mitotic regulation by vitisin A. Taken together, these results suggest that vitisin A inhibits adipocyte differentiation through preadipocyte cell cycle arrest.
Kim
Soon-hee
SH
Korea Food Research Institute, Functional Food Research Center, San 46-1, Baekhyun-dong, Bundang-ku, Songnam, Kyungki-do 463-746, Republic of Korea.
Park
Hee-Sook
HS
Lee
Myoung-su
MS
Cho
Yong-Jin
YJ
Kim
Young-Sup
YS
Hwang
Jin-Taek
JT
Sung
Mi Jeong
MJ
Kim
Myung Sunny
MS
Kwon
Dae Young
DY
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D019440:Anti-Obesity Agents; D001572:Benzofurans; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D010636:Phenols; D016160:Retinoblastoma Protein; D013267:Stilbenes; C412469:vitisin A