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马林酸通过调节 Sirt1/AMPK 信号通路来预防肥胖诱导的非酒精性脂肪肝病。

Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

机构信息

Division of Basic Medical Sciences, Department of Nursing, Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan.

Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.

出版信息

FASEB J. 2019 Nov;33(11):11791-11803. doi: 10.1096/fj.201900413RRR. Epub 2019 Jul 30.

Abstract

Maslinic acid is a pentacyclic triterpenoid that is distributed in the peel of olives. Previous studies found that maslinic acid inhibited inflammatory response and antioxidant effects. We investigated whether maslinic acid ameliorates nonalcoholic fatty liver disease in mice with high-fat-diet (HFD)-induced obesity and evaluated the regulation of lipogenesis in hepatocytes. Male C57BL/6 mice fed a normal diet or HFD (60% fat, w/w) were tested for 16 wk. After the fourth week, mice were injected intraperitoneally with maslinic acid for 12 wk. In another experiment, HepG2 cells were treated with oleic acid to induce lipid accumulation or maslinic acid to evaluate lipogenesis. Maslinic acid significantly reduced body weight compared with HFD-fed mice. Maslinic acid reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis. Furthermore, serum glucose, leptin, and free fatty acid concentrations significantly reduced, but the serum adiponectin concentration was higher, in the maslinic acid group than in the HFD group. In liver tissue, maslinic acid suppressed transcription factors involved in lipogenesis and increased adipose triglyceride lipase. , maslinic acid decreased lipogenesis by activating AMPK. These findings suggest that maslinic acid acts against hepatic steatosis by regulating enzyme activity involved in lipogenesis, lipolysis, and fatty acid oxidation in the liver.-Liou, C.-J., Dai, Y.-W., Wang, C.-L., Fang, L.-W., Huang, W.-C. Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

摘要

齐墩果酸是一种五环三萜,分布于橄榄皮中。先前的研究发现齐墩果酸具有抑制炎症反应和抗氧化作用。我们研究了齐墩果酸是否可以改善高脂肪饮食(HFD)诱导肥胖小鼠的非酒精性脂肪性肝病,并评估了其对肝细胞脂肪生成的调节作用。雄性 C57BL/6 小鼠给予正常饮食或 HFD(60%脂肪,w/w)喂养 16 周。第 4 周后,小鼠腹腔内注射齐墩果酸 12 周。在另一项实验中,用油酸处理 HepG2 细胞以诱导脂质积累,或用齐墩果酸处理以评估脂肪生成。与 HFD 喂养的小鼠相比,齐墩果酸显著降低了体重。齐墩果酸降低了肝重和肝脂质积累,改善了肝细胞脂肪变性。此外,与 HFD 组相比,齐墩果酸组血清葡萄糖、瘦素和游离脂肪酸浓度显著降低,而血清脂联素浓度升高。在肝组织中,齐墩果酸抑制了参与脂肪生成的转录因子,并增加了脂肪甘油三酯脂肪酶。研究表明,齐墩果酸通过激活 AMPK 来减少脂肪生成。这些发现表明,齐墩果酸通过调节肝脏脂肪生成、脂肪分解和脂肪酸氧化过程中涉及的酶活性来对抗肝脂肪变性。

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