肥胖引起的肠道微生物代谢物通过衰老的秘密促进肝癌
Shin Yoshimoto1, Tze Mun Loo, Koji Atarashi
1Division of Cancer Biology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
Nature
|June 28, 2013
概括
肥胖通过产生脱氧醇酸 (DCA) 的肠道细菌促进肝癌,这会在肝细胞中触发衰老相关分泌表型 (SASP). 阻止DCA或SASP可以预防肥胖小鼠的癌症发展.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
- 微生物学 微生物学
背景情况:
- 肥胖是一个日益严重的全球健康问题,也是各种癌症的重要危险因素,包括肝细胞癌 (HCC).
- 将肥胖与癌症发展联系在一起的精确分子机制仍然不完全理解.
- 了解这些机制对于制定有效的癌症预防和治疗策略至关重要.
研究的目的:
- 研究衰老相关分泌表型 (SASP) 在肥胖相关肝细胞癌 (HCC) 发展中的作用.
- 阐明连接肥胖,肠道微生物群和HCC的分子途径.
- 确定预防肥胖驱动的HCC的潜在治疗点.
主要方法:
- 利用食和遗传肥胖的小鼠模型.
- 研究了肠道微生物群变化的影响和脱氧胆酸 (DCA) 水平.
- 评估肝星细胞 (HSC) 和SASP在HCC发育中的作用.
- 检查了非酒精性脂肪肝炎患者的人类HCC组织.
主要成果:
- 肥胖会改变肠道微生物群,增加脱氧胆酸 (DCA) 水平,从而损害DNA.
- DCA在肝星细胞 (HSC) 中触发SASP,在肥胖小鼠中促进HCC的发展.
- 阻断DCA的产生或减少肠道细菌可以在肥胖小鼠中预防HCC.
- 抑制SASP或耗尽老化的HSC也抑制了HCC的发展.
- 在非酒精性脂肪肝炎患者的人类HCC组织中的HSC中观察到SASP.
结论:
- 肝星细胞 (HSC) 中的脱氧胆酸 (DCA) -SASP轴在与肥胖相关的HCC发展中发挥着关键作用.
- 准肠道微生物群,DCA或SASP是控制肥胖驱动的肝癌的有希望的策略.
- 研究结果表明,在肥胖和非酒精性脂肪肝炎的背景下,有保存的途径有助于人类HCC.
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