进化相关的宿主和微生物通路调节脂肪脱和
Bennett W Fox1, Maximilian J Helf1, Russell N Burkhardt1
1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
bioRxiv : the preprint server for biology
|September 11, 2023
概括
微生物群和宿主通路汇聚在NHR-49/PPARα上,以调节脂肪酸脱. 像becyp#1和bemeth#1这样的小分子激活脂肪-7表达,影响脂质代谢.
科学领域:
- 脂质代谢 脂质代谢是什么
- 分子生物学分子生物学
- 微生物学 微生物学
背景情况:
- 脂肪酸脱对于metazoan脂质代谢至关重要,影响膜脂质和信号分子.
- 营养条件和微生物群调节脱酶表达的机制在很大程度上是未知的.
- 核受体NHR-49/PPARα在调节脂质代谢方面发挥着关键作用.
研究的目的:
- 阐明调节脂质脱的机制,以响应内源性和微生物群衍生的信号.
- 确定参与控制C. elegans中脱酶表达的信号分子和途径.
主要方法:
- 在β-氧化突变体 (acdh-11) 上利用非向代谢学来识别累积的代谢物.
- 研究了核受体NHR-49/PPARα在调解代谢物诱导基因表达中的作用.
- 对具有与微生物化合物类似活性的内源代谢物进行选.
- 对微生物和内源性脂肪酸衍生物分析了不同的代谢途径.
主要成果:
- 鉴定了一种微生物衍生的β-cyclopropyl脂肪酸 (becyp#1),通过NHR-49.9激活stearoyl-CoA脱酶FAT-7表达.
- 发现一种具有类似活性的内源性β-甲基脂肪酸 (bemeth#1),来自宿主甲基转移酶fcmt-1.
- 证明贝西普#1和贝梅特#1通过不同的途径 (分别是β-氧化和α-氧化) 代谢.
- 表明becyp#1的生物合成依赖于细菌环氨酸合成酶,而bemeth#1来自宿主fcmt-1,可能是通过古代水平基因转移.
结论:
- 主体和微生物进化相关的途径汇聚在NHR-49/PPARα上,以调节脂肪脱.
- 来自宿主和微生物群的小分子信号在调节脂质代谢方面发挥着关键作用.
- 这项研究揭示了宿主微生物相互作用的新机制,用于调节重要的代谢过程.
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