Transcriptomics Reveals the Mechanism of Rosa roxburghii Tratt Ellagitannin in Improving Hepatic Lipid Metabolism Disorder in db/db Mice

A complex metabolic disorder, type 2 diabetes, was investigated to explore the impact of ellagitannin, derived from Rosa roxburghii Tratt (RTT), on liver lipid metabolism disorders in db/db mice. The findings demonstrated that both RTT ellagitannin (C1) and RTT ellagic acid (C4) considerably decelerated body mass gain in db/db mice, significantly decreased fasting blood glucose (FBG) levels, and mitigated the aggregation of hepatic lipid droplets. At LDL-C levels, C1 performed substantially better than the C4 group, exhibiting no significant difference compared to the P (positive control) group. An RNA-seq analysis further disclosed that 1245 differentially expressed genes were identified in the livers of experimental mice following the C1 intervention. The GO and KEGG enrichment analysis revealed that, under ellagitannin intervention, numerous differentially expressed genes were significantly enriched in fatty acid metabolic processes, the PPAR signaling pathway, fatty acid degradation, fatty acid synthesis, and other lipid metabolism-related pathways. The qRT-PCR and Western blot analysis results indicated that RTT ellagitannin notably upregulated the gene and protein expression levels of peroxisome proliferator-activated receptor alpha (PPAR alpha) and peroxisome proliferator-activated receptor gamma (PPAR gamma). In contrast, it downregulated the gene and protein expression levels of sterol regulatory element-binding protein (SREBP), recombinant fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC). Therefore, RTT ellagitannin can activate the PPAR signaling pathway, inhibit fatty acid uptake and de novo synthesis, and ameliorate hepatic lipid metabolism disorder in db/db mice, thus potentially aiding in maintaining lipid homeostasis in type 2 diabetes.

Automated summary

This study investigated the effects of ellagitannin from Rosa roxburghii Tratt on liver lipid metabolism disorder in db/db mice with type 2 diabetes. The results showed that ellagitannin significantly reduced body weight gain, decreased fasting blood glucose levels, and mitigated hepatic lipid droplet accumulation. RNA-seq analysis revealed differentially expressed genes and enrichment in fatty acid metabolic processes and other lipid metabolism-related pathways. Furthermore, ellagitannin upregulated the expression of PPAR alpha and PPAR gamma, while downregulating the expression of SREBP, FASN, and ACC. These findings suggest that ellagitannin can improve hepatic lipid metabolism disorder and potentially maintain lipid homeostasis in type 2 diabetes.