Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation

• Published in: International Journal of Obesity 2013-06, Vol.37 (6), p.881-884
• Main Authors: Choi, Y, Um, S-J, Park, T
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells - drug effects; 3T3-L1 Cells - metabolism; 631/443/319/1642/393; 631/92/349; 631/92/609; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipogenesis - drug effects; Animals; Anti-Obesity Agents - pharmacology; Apoptosis; Biological and medical sciences; Brassica; Cancer; Cancer cells; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cyclin-dependent kinases; Diet; Epidemiology; Federal regulation; Health aspects; Health Promotion and Disease Prevention; Humans; Indole; Indoles - pharmacology; Internal Medicine; Kinases; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Mice; Mice, Inbred C57BL; Natural products; Nutrition; Obesity; Obesity - drug therapy; Obesity - metabolism; Proteins; Public Health; Reverse Transcriptase Polymerase Chain Reaction; short-communication; Signal Transduction - drug effects; Sirtuin 1 - drug effects; Sirtuin 1 - metabolism; Vegetables
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2012.158

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 NAD + -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/EBPα, PPARγ2, 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.