果糖通过营养感应的 ghrelin 受体诱导巨细胞和微质细胞的炎症激活
Zheng Shen1, Zeyu Liu1, Hongying Wang1
1Department of Nutrition, Texas A&M University, College Station, Texas, USA.
概括
高果糖玉米糖 (HFCS) 的消费通过激活免疫细胞中的生长激素分泌受体 (GHSR) 来触发炎症. 准GHSR可能提供一种治疗策略来对抗果糖诱导的炎症性疾病.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢性疾病 代谢性疾病
- 分子生物学分子生物学
背景情况:
- 高果糖玉米糖 (HFCS) 消费与炎症有关,但直接机制尚不清楚.
- 增长激素分泌受体 (GHSR) 参与营养感应,并且以前已经表明可以调节HFCS诱导的炎症.
- 巨细胞和小质细胞是关键的先天性免疫细胞,控制了外围组织和大脑的炎症反应.
研究的目的:
- 调查GHSR是否在暴露于果糖时自主调节巨细胞和微质细胞的促炎激活.
- 确定GHSR在果糖运输,新陈代谢和随后的炎症信号通路中的作用.
主要方法:
- 使用CRISPR-Cas9基因编辑,在RAW 264.7巨细胞和IMG微质细胞中创建GHSR删除突变.
- 细胞在24小时内接受了同等度的果糖或葡萄糖的治疗.
- 分析了GHSR的mRNA和蛋白质表达,促炎细胞因子 (Il1β,Il6,Tnfα) 和信号通路组件.
主要成果:
- 果糖暴露增加了巨细胞和微质细胞的GHSR和促炎性细胞因子表达.
- 删除GHSR突变体显著减少了对果糖的炎症反应.
- 发现GHSR调节果糖的运输和新陈代谢,通过CREB-AKT-NF-κB和p38 MAPK通路调节炎症.
结论:
- 果糖在巨细胞和微质细胞中直接激活GHSR,诱导炎症.
- GHSR是果糖诱导的炎症激活的关键调解者.
- 准GHSR是一种潜在的治疗策略,可以减轻含果糖食品的免疫毒性.
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