title: Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte  differentiation.
abstract: Indole-3-carbinol (I3C), a natural product of Brassica vegetables such as broccoli and cabbage, inhibits proliferation and induces apoptosis in various cancer cells. I3C has recently received attention as a possible anti-obesity agent. However, how I3C interacts with specific targets in the pathways involved in obesity and metabolic disorders is unknown. Silent mating type information regulation 2 homolog 1 (SIRT1), a NADþ-dependent deacetylase sirtuin, has recently emerged as a novel therapeutic target for metabolic diseases. Herein, we report that I3C is a potent, specific SIRT1 activator efficacious in cultured 3T3-L1 cell lines. A pull-down assay showed that I3C binds to SIRT1. To assess the significance of this binding, we determined whether I3C could activate SIRT1 deacetylase activity in a cell-free system. We found that I3C binds to SIRT1 and activates SIRT1 deacetylase activity in 3T3-L1 cells. In addition, I3C did not inhibit adipocyte differentiation in 3T3-L1 cells in which SIRT1 was knockdowned. Further, reverse transcriptase polymerase chain reaction analysis showed that I3C treatment reduced mRNA levels of adipogenic genes that encode for C/EBPa, PPARg2, FAS, and aP2 in 3T3-L1 cells but not in SIRT1 knockdown cells. Overall, these results suggested that I3C ameliorates adipogenesis by activating SIRT1 in 3T3-L1 cells.
authors.affiliation: Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
authors.forename: S J
authors.initials: SJ
authors.lastname: Um
authors.forename: T
authors.initials: T
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D007211:Indoles; C016517:indole-3-carbinol; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1