Research Paper Volume 11, Issue 21 pp 9461—9477

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

Huihui Ren 1, , Dan Wang 1, , Lu Zhang 1, , Xiaonang Kang 1, , Yaling Li 1, , Xinrong Zhou 1, , Gang Yuan 1, ,

  • 1 Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China

received: July 23, 2019 ; accepted: October 21, 2019 ; published: November 7, 2019 ;

https://doi.org/10.18632/aging.102396
How to Cite

Copyright © 2019 Ren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Abbreviations

CAT: catalpol; NAFLD: non-alcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; HFD: high-fat diet; NCD: normal chow diet; STZ: streptozocin; TC: cholesterol; TG: triglyceride; AMPK: AMP-activated protein kinase; TFEB: transcription factor EB; FBS: fetal bovine serum; PA: palmitate; CQ: chloroquine; CC: compound C; SQSTM1: sequestosome 1; H&E: hematoxylin and eosin; Lamp1: lysosomal-associated membrane protein 1; AST: aspartate transaminase; ALT: alanine transaminase.