Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (7): 28-34.doi: 10.6040/j.issn.1671-7554.0.2025.1179

• Preclinical Medicine • Previous Articles     Next Articles

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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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

CLC Number: 

  • Q547
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[1] WANG Tengwei, LIN Hui, ZHANG Mingxiang, SUN Jinpeng, ZHANG Daolai. P19 activates the Gq pathway of GPR56 to promote browning of beige adipose [J]. Journal of Shandong University (Health Sciences), 2024, 62(3): 20-27.
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