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3,3'-二吲哚甲烷通过靶向 USP2 活性抑制前脂肪细胞的脂肪生成来抑制高脂肪饮食诱导的肥胖。

3,3'-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity.

机构信息

Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.

Department of Food Science, Purdue University, West Lafayette, IN, USA.

出版信息

Mol Nutr Food Res. 2017 Oct;61(10). doi: 10.1002/mnfr.201700119. Epub 2017 Jul 18.

DOI:10.1002/mnfr.201700119
PMID:28586165
Abstract

SCOPE

Indole-3-carbinol (I3C), a derivative abundant in cruciferous vegetables such as cabbage, is well known for its various health benefits such as chemo-preventive and anti-obesity effects. I3C is easily metabolized to 3,3'-diindolylmethane (DIM), a more stable form, in acidic conditions of the stomach. However, the anti-obesity effect of DIM has not been investigated clearly. We sought to investigate the effect of DIM on diet-induced obesity and to elucidate its underlying mechanisms.

METHODS AND RESULTS

High-fat diet (HFD)-fed obese mouse and MDI-induced 3T3-L1 adipogenesis models were used to study the effect of DIM. We observed that the administration of DIM (50 mg/kg BW) significantly suppressed HFD-induced obesity, associated with a decrease in adipose tissue. Additionally, we observed that DIM treatment (40 and 60 μM), but not I3C treatment, significantly inhibited MDI-induced adipogenesis by reducing the levels of several adipogenic proteins such as PPAR-γ and C/EBPα. DIM, but not I3C, suppressed cell cycle progression in the G1 phase, which occurred in the early stage of adipogenesis, inducing post-translational degradation of cyclin D1 by inhibiting ubiquitin specific peptidase 2 (USP2) activities.

CONCLUSION

Our findings indicate that cruciferous vegetables, which can produce DIM as a metabolite, have the potential to prevent or treat chronic obesity.

摘要

范围

吲哚-3-甲醇(I3C)是一种在卷心菜等十字花科蔬菜中含量丰富的衍生物,以其多种健康益处而闻名,如化学预防和抗肥胖作用。I3C 在胃的酸性条件下很容易代谢为 3,3'-二吲哚甲烷(DIM),这是一种更稳定的形式。然而,DIM 的抗肥胖作用尚未得到明确的研究。我们试图研究 DIM 对饮食诱导肥胖的影响,并阐明其潜在机制。

方法和结果

使用高脂肪饮食(HFD)喂养的肥胖小鼠和 MDI 诱导的 3T3-L1 脂肪生成模型来研究 DIM 的作用。我们观察到,DIM(50mg/kgBW)的给药显著抑制了 HFD 诱导的肥胖,伴随着脂肪组织的减少。此外,我们观察到 DIM 处理(40 和 60μM),而不是 I3C 处理,通过降低几种脂肪生成蛋白的水平,如 PPAR-γ 和 C/EBPα,显著抑制了 MDI 诱导的脂肪生成。DIM,但不是 I3C,抑制了细胞周期在 G1 期的进展,这发生在脂肪生成的早期阶段,通过抑制泛素特异性肽酶 2(USP2)的活性来诱导 cyclin D1 的翻译后降解。

结论

我们的发现表明,十字花科蔬菜可以作为代谢物产生 DIM,具有预防或治疗慢性肥胖的潜力。

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