School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China.
The Key Laboratory of Plant Resources Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering and College of Life Sciences, Guizhou University, Guiyang 550025, China.
Nutrients. 2023 Sep 28;15(19):4187. doi: 10.3390/nu15194187.
A complex metabolic disorder, type 2 diabetes, was investigated to explore the impact of ellagitannin, derived from 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 (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ). 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.
一种复杂的代谢紊乱疾病，即 2 型糖尿病，被研究以探索鞣花单宁（来源于 Tratt，RTT）对 db/db 小鼠肝脏脂质代谢紊乱的影响。研究结果表明，RTT 鞣花单宁（C1）和 RTT 鞣花酸（C4）都能显著减缓 db/db 小鼠的体重增加，显著降低空腹血糖（FBG）水平，并减轻肝内脂质滴的聚集。在 LDL-C 水平上，C1 组的表现明显优于 C4 组，与阳性对照组（P）相比无显著差异。RNA-seq 分析进一步揭示，在 C1 干预后，实验小鼠肝脏中鉴定出 1245 个差异表达基因。GO 和 KEGG 富集分析显示，在鞣花单宁干预下，大量差异表达基因在脂肪酸代谢过程、过氧化物酶体增殖物激活受体信号通路、脂肪酸降解、脂肪酸合成和其他脂质代谢相关通路中显著富集。qRT-PCR 和 Western blot 分析结果表明，RTT 鞣花单宁显著上调了过氧化物酶体增殖物激活受体α（PPARα）和过氧化物酶体增殖物激活受体γ（PPARγ）的基因和蛋白表达水平。相反，它下调了固醇调节元件结合蛋白（SREBP）、重组脂肪酸合酶（FASN）和乙酰辅酶 A 羧化酶（ACC）的基因和蛋白表达水平。因此，RTT 鞣花单宁可以激活 PPAR 信号通路，抑制脂肪酸摄取和从头合成，改善 db/db 小鼠的肝脂质代谢紊乱，从而有助于维持 2 型糖尿病患者的脂质平衡。
