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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8346235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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