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山东大学学报 (医学版) ›› 2026, Vol. 64 ›› Issue (7): 28-34.doi: 10.6040/j.issn.1671-7554.0.2025.1179

• 基础医学 • 上一篇    下一篇

神经酰胺C16∶0激活甲酰肽受体2调控棕色脂肪组织产热的转录组学分析

张明祥1,2,吕琳2,林慧2,孙金鹏2,张道来1   

  1. 1.山东医药大学药学院, 山东 烟台 264003;2.山东大学基础医学院, 山东 济南 250012
  • 出版日期:2026-07-10 发布日期:2026-07-21
  • 通讯作者: 张道来. E-mail:dlzhang@bzmc.edu.cn孙金鹏. E-mail:sunjinpeng@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(32130055,82371629,82304583);山东省自然科学基金(ZR2024MC198)

C16∶0 ceramide activates formyl peptide receptor 2 to regulate adipose tissue thermogenesis: a transcriptomics-based analysis

ZHANG Mingxiang1,2, LYU Lin2, LIN Hui2, SUN Jinpeng2, ZHANG Daolai1   

  1. 1. School of Pharmacy, Shandong Medical and Pharmaceutical University, Yantai 264003, Shandong, China;
    2. Department of Basic Medical Sciences, Shandong University, Jinan 250012, Shandong, China
  • Online:2026-07-10 Published:2026-07-21

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摘要： 目的 探讨神经酰胺C16∶0激活甲酰肽受体2(formyl peptide receptor 2, FPR2)调控棕色脂肪组织(brown adipose tissue, BAT)产热的下游关键基因及其分子机制。 方法 以小鼠BAT为研究对象,使用神经酰胺C16∶0 ［10 mg/(kg·d)］和空载体连续3 d给小鼠进行腹腔注射,之后在4 ℃环境中暴露24 h。采用Western blotting和qPCR技术检测BAT中解偶联蛋白1(uncoupling protein 1, UCP1)的表达水平。利用转录组学测序技术进一步筛选神经酰胺C16∶0调控BAT产热的相关基因,并通过qPCR法对筛选的基因进行验证。 结果 神经酰胺C16∶0可以降低BAT中UCP1的mRNA表达水平［(0.608±0.066)vs.(1.001±0.033), F=3.879, P=0.017］和蛋白水平［(0.725±0.036)vs.(1.000±0.043), F=1.365, P=0.008］;转录组学测序共筛选出909个差异表达基因(620个上调,289个下调)。GO和KEGG富集分析显示,神经酰胺C16∶0显著下调过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptor, PPAR)和叉头框蛋白O(forkhead box O, FOXO)信号通路,从中筛选出7个基因(SLC27A2、HMGCS2、EHHADH、PCK1、IRS2、SGK2、PLK3),在Sox2-CreER+/-Fpr2fl/fl小鼠中验证发现,其表达受神经酰胺C16∶0-FPR2轴特异性调控。 结论 神经酰胺C16∶0通过FPR2下调小鼠BAT中UCP1表达,其机制与PPAR信号通路和FOXO信号通路密切相关,通过调控SLC27A2、HMGCS2、EHHADH、PCK1、IRS2、SGK2和PLK3基因表达抑制BAT产热。

关键词: 甲酰肽受体2, 神经酰胺C16∶0, 信号转导通路, 棕色脂肪组织产热

Abstract: Objective To investigate the key downstream genes and molecular mechanisms through which C16∶0 ceramide activates formyl peptide receptor 2(FPR2)to regulate thermogenesis in brown adipose tissue(BAT). Methods Using mouse BAT as the research model, mice were intraperitoneally injected with C16∶0 ceramide ［10 mg/(kg·d)］ or vehicle for three consecutive days, followed by exposure to 4 ℃ for 24 h. The expression level of uncoupling protein 1(UCP1)in BAT was detected by Western blotting and qPCR. Transcriptome sequencing was further employed to identify genes involved in C16∶0 ceramide-mediated regulation of BAT thermogenesis, and the screened genes were validated by qPCR. Results C16∶0 ceramide significantly reduced both the mRNA expression level of UCP1 in BAT ［(0.608±0.066)vs.(1.001±0.033), F=3.879, P=0.017 ［and its protein level ［(0.725±0.036)vs.(1.000±0.043), F=1.365, P=0.008］. Transcriptome sequencing identified 909 differentially expressed genes(620 up-regulated and 289 down-regulated). GO and KEGG enrichment analyses showed that C16∶0 ceramide significantly down-regulated the peroxisome proliferators-activated receptor(PPAR)and forkhead box O(FOXO)signaling pathways, from which seven genes(SLC27A2、HMGCS2、EHHADH、PCK1、IRS2、SGK2, and PLK3)were selected. Validation in Sox2-CreER+/-Fpr2fl/fl mice revealed that their expression was specifically regulated by the C16∶0 ceramide-FPR2 axis. Conclusion C16∶0 ceramide down-regulates UCP1 expression in mouse BAT via FPR2. This mechanism is closely associated with the PAR and FoxO signaling pathways, and inhibits BAT thermogenesis by regulating the expression of SLC27A2,HMGCS2,EHHADH,PCK1,IRS2,SGK2 and PLK3.

Key words: Formyl peptide receptor 2, C16∶0 ceramide, Signal transduction pathway, Brown adipose tissue thermogenesis

中图分类号: 

  • Q547
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[1] 王腾威,林慧,张明祥,孙金鹏,张道来. P19激活GPR56的Gq通路促进米色脂肪棕色化[J]. 山东大学学报 (医学版), 2024, 62(3): 20-27.
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