高脂肪饮食增强了肠道原体的干性和瘤性
Semir Beyaz1,2, Miyeko D Mana1, Jatin Roper1,3
1The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, Massachusetts 02139, USA.
Nature
|March 4, 2016
概括
高脂肪饮食通过PPAR-δ激活增加肠道干细胞数量和功能. 这种途径还增强了原生细胞的瘤形成潜力,
科学领域:
- 胃肠病学
- 细胞生物学
- 代谢疾病
背景情况:
- 饮食对组织干细胞和原生细胞功能的影响在很大程度上尚未研究.
- 肥胖与包括癌症在内的各种健康并发症有关, 但干细胞的潜在机制尚不清楚.
研究的目的:
- 调查促肥胖饮食,特别是高脂肪饮食如何影响肠道干细胞和原始细胞功能.
- 阐明分子机制,特别是过氧体增殖器激活受体三角体 (PPAR-δ) 在调解这些饮食影响中的作用.
- 评估饮食调节干细胞功能对瘤启动能力的影响.
主要方法:
- 在高脂肪饮食的小鼠中分析Lgr5(+) 肠干细胞数量和功能.
- 在肠道干细胞和祖细胞中研究过氧体增殖器激活受体三角体 (PPAR-δ) 的表达.
- PPAR-δ的药理活性及其对肠道器官培养物的作用.
- 在缺少 Apc 瘤抑制剂的原始细胞中强制发出 PPAR-δ 信号后评估瘤形成.
主要成果:
- 高脂肪饮食 (HFD) 的摄入增加了Lgr5(+) 肠干细胞的数量和功能.
- 在肠道干细胞和祖细胞中诱导了显著的PPAR-δ特征.
- 药理上的PPAR-δ激活模仿了HFD效应,以PPAR-δ依赖的方式增强了器官的自我更新.
- 在原生细胞中强化PPAR-δ信号促进了体内瘤的形成,特别是在APC损失后.
结论:
- 通过高脂肪饮食诱导的肥胖通过PPAR-δ激活增加了肠道干细胞和原始细胞的功能.
- 通过饮食调节的肠道原体中的PPAR-δ信号可以驱动瘤发作,特别是在瘤抑制剂损失的背景下.
- 这些发现表明饮食习惯,干细胞生物学和肠道癌症发展之间存在联系.
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