卡路里限制激活了胃的Notch-FOXO1通路,以扩大 ghrelin 细胞
Wendy M McKimpson1,2, Sophia Spiegel1,2, Maria Mukhanova1,2
1Department of Medicine, Division of Endocrinology, Columbia University, New York, NY, USA.
The Journal of cell biology
|July 3, 2024
概括
卡路里限制通过Notch和FOXO1通路影响干细胞和前代细胞,从而增加胃内分泌细胞数量,包括 ghrelin 细胞. 这一发现澄清了卡路里限制.
科学领域:
- 胃肠病学 胃肠病学
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 已知卡路里限制 (CR) 可以延长寿命,但其对胃肠道的具体影响尚未完全理解.
- 胃肠道拥有多样化的细胞群,包括产生激素的内分泌细胞,它们在消化和新陈代谢中起着至关重要的作用.
研究的目的:
- 研究卡路里限制对胃内分泌细胞群及其潜在调节机制的影响.
- 阐明诺奇信号通路和FOXO1在调解CR诱导的胃干细胞和祖细胞变化的作用.
主要方法:
- 使用卡路里限制小鼠模型和初级细胞培养.
- 雇佣了基因报告器和药理抑制剂 (DAPT,PF-03084014) 来研究Notch信号.
- 研究了FOXO1激活和 ghrelin受体对抗性 (GHRP-6) 的作用.
- 评估了蒂尔泽帕提德对胃内分泌细胞的影响.
主要成果:
- 卡路里限制增加了小鼠胃中染色素A阳性和 ghrelin 阳性细胞的数量.
- 这些增加与Lgr5+干细胞和Neurog3+内分泌前体细胞的变异增殖有关,由Notch信号调节.
- CR减少了胃Lgr5+干细胞,但以依赖于Notch的方式增加了FOXO1/Neurog3+原始子群.
- FOXO1激活促进了独立于Notch的内分泌分化;Notch抑制或 ghrelin对抗逆转了CR效应.
结论:
- 卡路里限制促进胃内分泌细胞的分化,通过一种涉及Notch-dependent和FOXO1-regulated通路的机制.
- 这些发现突出了胃内的特定细胞适应,以应对饮食限制,影响激素的产生.
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