Bioinformatics investigation for lipid accumulation mechanisms in the liver of old obese mice treated with celastrol

Abstract Background Hypoglycemic and hypolipidemic effects of celastrol were receiving increasing attentions. Celastrol as a triterpene has been reported to ameliorate age-associated weight gain by modulating circadian rhythms, but its linked molecular mechanism is obscure. This study aimed to investigate the mechanism of celastrol on liver metabolism for the elderly. A total of 100 μg/kg celastrol was given to old ICR mice for a period of 10 days. Histological and lipid metabolism analyses were performed to confirm the benefit of celastrol on liver fatty acid metabolism. Transcriptome analysis and molecular docking were used to explore the hepatoprotection mechanism of celastrol. Results We found that celastrol intervention improved glycolipid metabolism in the liver of aging ICR mice. Transcriptome analysis of liver revealed that celastrol can significantly reduced the expression levels of 45 genes (log2(FC) > 2) in liver of old mice, closely related to MAPK signaling pathway, TNF-α signaling pathway and NF-κB signaling pathway. Molecular docking results indicated three genes (Gadd45a, Atf3, and Rcan1) upregulated at the transcriptional level in old mice have high binding energy to celastrol (− 5.02 kcal/mol, − 7.58 kcal/mol, − 9.61 kcal/mol). Conclusions This study suggested that MAPK and NF-κB signaling pathway might be the main way for the hepatoprotective effect of celastrol in aging mice. Graphical Abstract