Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, 1 Yixueyuan Road, Chongqing Medical University, Yuzhong District, Chongqing, 400016, P. R. China.
Department of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, 1 Yixueyuan Road, Chongqing Medical University, Yuzhong District, Chongqing, 400016, P. R. China.
Mol Nutr Food Res. 2023 Jun;67(12):e2200533. doi: 10.1002/mnfr.202200533. Epub 2023 May 8.
The mechanisms of oleanolic acid (OA) regulating hepatic sterol regulatory element-binding protein (SREBP) 1c/stearoyl-CoA desaturase (SCD) 1 pathway to ameliorate fructose-induced hepatosteatosis are investigated.
Rats treated with 10% w/v fructose solution are co-administered by OA for 5 weeks, and then sacrifice after fasting for 14 h. OA reverses the fructose-induced increase in hepatic triglyceride (TG) content and downregulates Scd1 mRNA expression. However, two upstream transcription factors, ChREBP and SREBP1c, remain at normal levels with or without fructose and/or OA. In vivo and in vitro studies using SREBP1c mice and HepG2 cell models show that OA also inhibits SCD1 gene overexpression and high hepatic TG levels induced by fructose. On the other hand, in SCD1 mice, when the fructose diet is supplemented with high levels of oleic acid (OLA) to compensate for the deficiency of SCD1, OA inhibits hepatic SREBP1c and lipogenic gene expression and reduces hepatic OLA (C18:1) production to improve fructose and/or OLA induced liver lipid deposition. Furthermore, OA promotes PPARα and AMPK to enhance fatty acid oxidation in fructose + OLA-fed SCD1 mice.
OA may inhibit SCD1 gene expression to ameliorate fructose-induced hepatosteatosis through SREBP1c-dependent and -independent mechanisms.
研究了齐墩果酸（OA）调节肝固醇调节元件结合蛋白（SREBP）1c/硬脂酰辅酶 A 去饱和酶（SCD）1 途径改善果糖诱导的肝脂肪变性的机制。
用 10%w/v 果糖溶液处理大鼠，并用 OA 共同给药 5 周，然后禁食 14 h 后处死。OA 逆转了果糖诱导的肝甘油三酯（TG）含量增加，并下调了 Scd1 mRNA 表达。然而，两个上游转录因子 ChREBP 和 SREBP1c 在有或没有果糖和/或 OA 的情况下仍保持正常水平。使用 SREBP1c 小鼠和 HepG2 细胞模型的体内和体外研究表明，OA 还抑制了果糖诱导的 SCD1 基因过表达和肝 TG 水平升高。另一方面，在 SCD1 小鼠中，当果糖饮食补充高水平的油酸（OLA）以弥补 SCD1 的缺乏时，OA 抑制肝 SREBP1c 和脂肪生成基因表达，并减少肝 OLA（C18：1）的产生，以改善果糖和/或 OLA 诱导的肝脂肪沉积。此外，OA 促进 PPARα 和 AMPK 增强果糖+OLA 喂养的 SCD1 小鼠中的脂肪酸氧化。
OA 可能通过 SREBP1c 依赖和非依赖机制抑制 SCD1 基因表达，从而改善果糖诱导的肝脂肪变性。
