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

Y. Choi, S. J. Um, Taesun Park

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)881-884
Number of pages4
JournalInternational Journal of Obesity
Volume37
Issue number6
DOIs
Publication statusPublished - 2013 Jun 1

Fingerprint

Adipocytes
3T3-L1 Cells
Brassica
Sirtuin 1
indole-3-carbinol
Anti-Obesity Agents
Adipogenesis
Cell-Free System
Metabolic Diseases
Biological Products
Reverse Transcriptase Polymerase Chain Reaction
Vegetables
NAD
Cultured Cells
Obesity
Apoptosis
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

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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 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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Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation. / Choi, Y.; Um, S. J.; Park, Taesun.

In: International Journal of Obesity, Vol. 37, No. 6, 01.06.2013, p. 881-884.

Research output: Contribution to journalArticle

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