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Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy

Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a pote...

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Autores principales: Zhang, Dan, Ma, Yicheng, Liu, Jianjun, Deng, Yi, Zhou, Bo, Wen, Yu, Li, Mingke, Wen, Daiyan, Ying, Yunyan, Luo, Sufeng, Shi, Chunjing, Pu, Guangyu, Miao, Yinglei, Zou, Chenggang, Chen, Yuanli, Ma, Lanqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346235/
https://www.ncbi.nlm.nih.gov/pubmed/34366846
http://dx.doi.org/10.3389/fphar.2021.689111
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author Zhang, Dan
Ma, Yicheng
Liu, Jianjun
Deng, Yi
Zhou, Bo
Wen, Yu
Li, Mingke
Wen, Daiyan
Ying, Yunyan
Luo, Sufeng
Shi, Chunjing
Pu, Guangyu
Miao, Yinglei
Zou, Chenggang
Chen, Yuanli
Ma, Lanqing
author_facet Zhang, Dan
Ma, Yicheng
Liu, Jianjun
Deng, Yi
Zhou, Bo
Wen, Yu
Li, Mingke
Wen, Daiyan
Ying, Yunyan
Luo, Sufeng
Shi, Chunjing
Pu, Guangyu
Miao, Yinglei
Zou, Chenggang
Chen, Yuanli
Ma, Lanqing
author_sort Zhang, Dan
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.
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spelling pubmed-83462352021-08-07 Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy Zhang, Dan Ma, Yicheng Liu, Jianjun Deng, Yi Zhou, Bo Wen, Yu Li, Mingke Wen, Daiyan Ying, Yunyan Luo, Sufeng Shi, Chunjing Pu, Guangyu Miao, Yinglei Zou, Chenggang Chen, Yuanli Ma, Lanqing Front Pharmacol Pharmacology Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD. Frontiers Media S.A. 2021-07-23 /pmc/articles/PMC8346235/ /pubmed/34366846 http://dx.doi.org/10.3389/fphar.2021.689111 Text en Copyright © 2021 Zhang, Ma, Liu, Deng, Zhou, Wen, Li, Wen, Ying, Luo, Shi, Pu, Miao, Zou, Chen and Ma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Dan
Ma, Yicheng
Liu, Jianjun
Deng, Yi
Zhou, Bo
Wen, Yu
Li, Mingke
Wen, Daiyan
Ying, Yunyan
Luo, Sufeng
Shi, Chunjing
Pu, Guangyu
Miao, Yinglei
Zou, Chenggang
Chen, Yuanli
Ma, Lanqing
Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
title Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
title_full Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
title_fullStr Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
title_full_unstemmed Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
title_short Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
title_sort metformin alleviates hepatic steatosis and insulin resistance in a mouse model of high-fat diet-induced nonalcoholic fatty liver disease by promoting transcription factor eb-dependent autophagy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346235/
https://www.ncbi.nlm.nih.gov/pubmed/34366846
http://dx.doi.org/10.3389/fphar.2021.689111
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