PUBLICATION
Imidazole propionate ameliorates lipid metabolism in adipocytes to attenuate high-fat diet-induced obesity via PPAR signaling pathway
- Authors
- Lin, C., Peng, Z., Du, J., Shan, X., Zhang, Z., Xu, L., Huang, S., Gao, J., Guo, X.
- ID
- ZDB-PUB-251108-9
- Date
- 2025
- Source
- Lipids in health and disease 24: 356356 (Journal)
- Registered Authors
- Keywords
- High-fat diet, Imidazole propionate, Lipid accumulation, Obesity, PPAR signaling pathway, Zebrafish
- MeSH Terms
-
- Adipocytes*/drug effects
- Adipocytes*/metabolism
- Animals
- Diet, High-Fat/adverse effects
- Gastrointestinal Microbiome/drug effects
- Humans
- Imidazoles*/pharmacology
- Lipid Metabolism*/drug effects
- Male
- Mice
- Mice, Inbred C57BL
- Obesity*/drug therapy
- Obesity*/etiology
- Obesity*/metabolism
- Obesity*/pathology
- Peroxisome Proliferator-Activated Receptors*/genetics
- Peroxisome Proliferator-Activated Receptors*/metabolism
- Propionates*/pharmacology
- Signal Transduction/drug effects
- Zebrafish
- PubMed
- 41204354 Full text @ Lipids Health Dis.
Citation
Lin, C., Peng, Z., Du, J., Shan, X., Zhang, Z., Xu, L., Huang, S., Gao, J., Guo, X. (2025) Imidazole propionate ameliorates lipid metabolism in adipocytes to attenuate high-fat diet-induced obesity via PPAR signaling pathway. Lipids in health and disease. 24:356356.
Abstract
Background Obesity is a global health concern linked to metabolic disorders and gut microbiota dysbiosis, particularly under high-fat diet (HFD) conditions. This study explores the role of imidazole propionate (ImP), a histidine-derived microbial metabolite, in regulating lipid metabolism and the development of obesity.
Methods Male C57BL/6 mice were fed either a chow diet or HFD for 15 weeks, followed by plasma metabolomic analysis, which revealed significant downregulation of ImP in obese mice. Functional assays were performed using zebrafish larvae and human adipocytes, with lipid accumulation assessed via Nile Red and Oil Red O staining. Transcriptomic sequencing and KEGG pathway analysis were used to investigate the underlying molecular mechanisms.
Results ImP treatment notably reduced lipid accumulation in both zebrafish larvae and human adipocytes. RNA-seq and protein expression analyses revealed that ImP suppressed peroxisome proliferator-activated receptor (PPAR) pathway key components, such as FABP4, ACSL4, and CEBPα.
Conclusions These findings demonstrate that ImP attenuates lipid accumulation by inhibiting the PPAR signaling pathway. As a gut microbial metabolite, ImP may offer therapeutic potential in preventing or treating HFD-induced obesity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping