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

International Journal of Obesity volume 37, pages 881–884 (2013)Cite this article

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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 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.

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References

  1. Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH . Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene 2001; 20: 2927–2936.

    Article  CAS  Google Scholar 

  2. Aggarwal BB, Ichikawa H . Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle 2005; 4: 1201–1215.

    Article  CAS  Google Scholar 

  3. Chang HP, Wang ML, Chan MH, Chiu YS, Chen YH . Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice. Nutrition 2011; 27: 463–470.

    Article  CAS  Google Scholar 

  4. Chang HP, Wang ML, Hsu CY, Liu ME, Chan MH, Chen YH . Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes. Int J Obes (Lond) 2011; 35: 1530–1538.

    Article  CAS  Google Scholar 

  5. Choi Y, Kim Y, Park S, Lee KW, Park T . Indole-3-carbinol prevents diet-induced obesity through modulation of multiple genes related to adipogenesis, thermogenesis or inflammation in the visceral adipose tissue of mice. J Nutr Biochem 2012. e-pub ahead of print 7 May 2012 doi: 10.1016/j.jnutbio.2011.12.005.

    Article  CAS  Google Scholar 

  6. Reagan-Shaw S, Nihal M, Ahmad N . Dose translation from animal to human studies revisited. FASEB J 2008; 22: 659–661.

    Article  CAS  Google Scholar 

  7. Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev 2005; 14: 1953–1960.

    Article  CAS  Google Scholar 

  8. Shimamoto K, Dewa Y, Ishii Y, Kemmochi S, Taniai E, Hayashi H et al. Indole-3-carbinol enhances oxidative stress responses resulting in the induction of preneoplastic liver cell lesions in partially hepatectomized rats initiated with diethylnitrosamine. Toxicology 2011; 283: 109–117.

    Article  CAS  Google Scholar 

  9. Haigis MC, Sinclair DA . Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol 2010; 5: 253–295.

    Article  CAS  Google Scholar 

  10. Fischer-Posovszky P, Kukulus V, Tews D, Unterkircher T, Debatin KM, Fulda S et al. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am J Clin Nutr 2010; 92: 5–15.

    Article  CAS  Google Scholar 

  11. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337–342.

    Article  CAS  Google Scholar 

  12. Murata M, Ide T, Hara K . Reciprocal responses to dietary diacylglycerol of hepatic enzymes of fatty acid synthesis and oxidation in the rat. Br J Nutr 1997; 77: 107–121.

    Article  CAS  Google Scholar 

  13. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R et al. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 2007; 26: 1913–1923.

    Article  CAS  Google Scholar 

  14. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23: 2369–2380.

    Article  CAS  Google Scholar 

  15. Zhang J . The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation. J Biol Chem 2007; 282: 34356–34364.

    Article  CAS  Google Scholar 

  16. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004; 429: 771–776.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare (#090282), Republic of Korea and by the SRC program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (#2012-0000643).

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Authors and Affiliations

  1. Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea

    Y Choi & T Park

  2. Department of Bioscience and Biotechnology/Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul, Republic of Korea

    S-J Um

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  1. Y Choi
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  2. S-J Um
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Correspondence to T Park.

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Supplementary Information accompanies the paper on International Journal of Obesity website

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Choi, Y., Um, SJ. & Park, T. Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation. Int J Obes 37, 881–884 (2013). https://doi.org/10.1038/ijo.2012.158

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