Catalpol induces autophagy and attenuates liver steatosis in ob/ob and high-fat diet-induced obese mice
Catalpol induces autophagy and attenuates liver steatosis in ob/ob and high-fat diet-induced obese mice
复制标题
梓醇诱导自噬并减轻 ob/ob 和高脂饮食诱导的肥胖小鼠的肝脏脂肪变性
DOI：
10.18632/aging.102396
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发表时间：
2019-11-15
期刊：
影响因子：
5.2
通讯作者：
Yuan, Gang
中科院分区：
文献类型：
--
作者：
Ren, Huihui;Wang, Dan;Yuan, Gang
自噬受损与非酒精性脂肪肝的发病机制有关。梓醇（Catalpol，CAT）是从地黄中提取的一种具有生物活性的化合物，它能改善肥胖小鼠的胰岛素抵抗和组织学NAFLD谱。在这里，我们研究了CAT对ob/ob和高脂饮食诱导的肥胖小鼠以及肝细胞中肝脂肪变性和自噬的影响。在ob/ob小鼠中，CAT降低了肝脏重量、肝脏甘油三酯和胆固醇含量、肝脏脂肪生成酶水平，并增加了脂肪酸氧化酶水平。此外，CAT给药增加了ob/ob小鼠中的LC 3-II水平并降低了SQSTM 1/P62水平。在高脂饮食诱导的小鼠中观察到CAT对肝脂肪变性和自噬的类似作用。此外，我们发现CAT刺激AMPK并增加肥胖小鼠和肝细胞中转录因子EB（TFEB）的核转位。AMPK的抑制完全阻断了CAT对TFEB核定位、肝自噬和肝脂肪变性的影响。这些研究结果表明，减少AMPK/TFEB依赖性自噬参与肥胖症肝脂肪变性的发病机制，CAT可能是治疗这种疾病的新的治疗候选者。
Impaired autophagy has been implicated in the pathogenesis of nonalcoholic fatty liver disease. Catalpol (CAT), a bioactive compound from Rehmannia (Di Huang) glutinosa, is known to ameliorate insulin resistance and the histological NAFLD spectrum in obese mice. Here, we investigated the effects of CAT on hepatic steatosis and autophagy in ob/ob and high-fat diet-induced obese mice, as well as in hepatocytes. In ob/ob mice, CAT reduced liver weight, liver triglyceride and cholesterol content, and hepatic lipogenic enzyme levels and increased fatty acid oxidase levels. In addition, CAT administration increased LC3-II levels and decreased SQSTM1/P62 levels in ob/ob mice. Similar effects on hepatic steatosis and autophagy were observed in high-fat diet-induced mice after administration of CAT. Additionally, we found that CAT stimulated AMPK and increased nuclear translocation of transcription factor EB (TFEB) in obese mice and hepatocytes. Inhibition of AMPK completely blocked the effects of CAT on TFEB nuclear localization, hepatic autophagy, and liver steatosis. These findings revealed that diminished AMPK/TFEB-dependent autophagy is involved in the pathogenesis of liver steatosis in obesity, and that CAT might be a novel therapeutic candidate for treatment of this condition.