Insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM), which is closely related to disorder of lipid metabolism. The study was designed to evaluate the effects of oleanolic acid (OA) on hepatic insulin resistance and underlying mechanisms in Lep(db)(/)(db) obese diabetic mice. db/db Mice were administered with OA (20mg/kg/day, i.p.) for two weeks. OA reduced body weight, liver weight, and fat weight, and protected liver morphology and function. OA decreased fasting blood glucose, improved glucose and insulin tolerance, enhanced insulin signaling and inhibited gluconeogenesis. In livers, mitochondrial biogenesis, ultrastructure and function were influenced, accompanied by increased cellular and mitochondrial ROS production. OA inhibited all these changes, in which process Nrf2-GCLc mediated stabilization of mitochondrial glutathione pool may be involved. Moreover, OA decreased serum triglyceride, total cholesterol, LDL, HDL, and free fatty acids, increased serum HDL, and reduced hepatic lipid accumulation. Furthermore, inflammatory condition in db/db mice was improved by OA, as evidenced by decreased level of IL-1 β, IL-6, and TNFα in circulation and in liver. The evidence suggests that OA improves hepatic insulin resistance through inhibition of mitochondrial ROS, hypolipidemic and anti-inflammatory effects. The effectiveness of OA leads to interesting therapeutic perspectives.

中文翻译：

---

齐墩果酸通过抗氧化剂，降血脂和抗炎作用改善肝胰岛素抵抗。

胰岛素抵抗是2型糖尿病（T2DM）的标志，它与脂质代谢紊乱密切相关。该研究旨在评估齐墩果酸（OA）对Lep（db）（/）（db）肥胖糖尿病小鼠的肝胰岛素抵抗及其潜在机制的影响。db / db小鼠接受OA（20mg / kg / day，ip）给药两周。OA减轻了体重，肝脏重量和脂肪重量，并保护了肝脏的形态和功能。OA可降低空腹血糖，改善葡萄糖和胰岛素耐受性，增强胰岛素信号传导并抑制糖异生。在肝脏中，线粒体的生物发生，超微结构和功能受到影响，并伴随着细胞和线粒体ROS产生的增加。OA抑制了所有这些变化，Nrf2-GCLc介导的线粒体谷胱甘肽池稳定可能参与其中。此外，OA降低血清甘油三酸酯，总胆固醇，LDL，HDL和游离脂肪酸，增加血清HDL，并减少肝脂质蓄积。此外，OA / OS改善了db / db小鼠的炎症，这可以通过循环和肝脏中IL-1β，IL-6和TNFα的降低来证明。证据表明，OA通过抑制线粒体ROS，降血脂和抗炎作用来改善肝胰岛素抵抗。OA的有效性带来了有趣的治疗前景。OA可改善db / db小鼠的炎症状况，这可以通过循环和肝脏中IL-1β，IL-6和TNFα的降低来证明。证据表明，OA通过抑制线粒体ROS，降血脂和抗炎作用来改善肝胰岛素抵抗。OA的有效性带来了有趣的治疗前景。OA可改善db / db小鼠的炎症状况，这可以通过循环和肝脏中IL-1β，IL-6和TNFα的降低来证明。证据表明，OA通过抑制线粒体ROS，降血脂和抗炎作用来改善肝胰岛素抵抗。OA的有效性带来了有趣的治疗前景。