Catalpol induces autophagy and attenuates liver steatosis in ob/ob and high-fat diet-induced obese mice

被引:51
作者
Ren, Huihui [1 ]
Wang, Dan [1 ]
Zhang, Lu [1 ]
Kang, Xiaonang [1 ]
Li, Yaling [1 ]
Zhou, Xinrong [1 ]
Yuan, Gang [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Endocrinol, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China
来源
AGING-US | 2019年 / 11卷 / 21期
基金
中国国家自然科学基金;
关键词
catalpol; nonalcoholic fatty liver disease; autophagy; AMPK; obesity; ACTIVATED PROTEIN-KINASE; INSULIN-RESISTANCE; DISEASE; MODULATORS; INDUCTION; PATHWAY;
D O I
10.18632/aging.102396
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:9461 / 9477
页数:17
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