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MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3

The etiology of numerous metabolic disorders is characterized by hepatic insulin resistance (IR). Uncertainty surrounds miR-34a’s contribution to high-fat-induced hepatic IR and its probable mechanism. The role and mechanism of miR-34a and its target gene ENO3 in high-fat-induced hepatic IR were exp...

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Autores principales: Wang, Yuanyuan, Zhao, Xue, Zhang, Liuchao, Yang, Chunxiao, Zhang, Kening, Gu, Zhuo, Ding, Haiyan, Li, Shuangshuang, Qin, Jian, Chu, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650923/
https://www.ncbi.nlm.nih.gov/pubmed/37960269
http://dx.doi.org/10.3390/nu15214616
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author Wang, Yuanyuan
Zhao, Xue
Zhang, Liuchao
Yang, Chunxiao
Zhang, Kening
Gu, Zhuo
Ding, Haiyan
Li, Shuangshuang
Qin, Jian
Chu, Xia
author_facet Wang, Yuanyuan
Zhao, Xue
Zhang, Liuchao
Yang, Chunxiao
Zhang, Kening
Gu, Zhuo
Ding, Haiyan
Li, Shuangshuang
Qin, Jian
Chu, Xia
author_sort Wang, Yuanyuan
collection PubMed
description The etiology of numerous metabolic disorders is characterized by hepatic insulin resistance (IR). Uncertainty surrounds miR-34a’s contribution to high-fat-induced hepatic IR and its probable mechanism. The role and mechanism of miR-34a and its target gene ENO3 in high-fat-induced hepatic IR were explored by overexpressing/suppressing miR-34a and ENO3 levels in in vivo and in vitro experiments. Moreover, as a human hepatic IR model, the miR-34a/ENO3 pathway was validated in patients with non-alcoholic fatty liver disease (NAFLD). The overexpression of hepatic miR-34a lowered insulin signaling and altered glucose metabolism in hepatocytes. In contrast, reducing miR-34a expression significantly reversed hepatic IR indices induced by palmitic acid (PA)/HFD. ENO3 was identified as a direct target gene of miR-34a. Overexpression of ENO3 effectively inhibited high-fat-induced hepatic IR-related indices both in vitro and in vivo. Moreover, the expression patterns of members of the miR-34a/ENO3 pathway in the liver tissues of NAFLD patients was in line with the findings of both cellular and animal studies. A high-fat-induced increase in hepatic miR-34a levels attenuates insulin signaling and impairs glucose metabolism by suppressing the expression of its target gene ENO3, ultimately leading to hepatic IR. The miR-34a/ENO3 pathway may be a potential therapeutic target for hepatic IR and related metabolic diseases.
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spelling pubmed-106509232023-10-31 MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3 Wang, Yuanyuan Zhao, Xue Zhang, Liuchao Yang, Chunxiao Zhang, Kening Gu, Zhuo Ding, Haiyan Li, Shuangshuang Qin, Jian Chu, Xia Nutrients Article The etiology of numerous metabolic disorders is characterized by hepatic insulin resistance (IR). Uncertainty surrounds miR-34a’s contribution to high-fat-induced hepatic IR and its probable mechanism. The role and mechanism of miR-34a and its target gene ENO3 in high-fat-induced hepatic IR were explored by overexpressing/suppressing miR-34a and ENO3 levels in in vivo and in vitro experiments. Moreover, as a human hepatic IR model, the miR-34a/ENO3 pathway was validated in patients with non-alcoholic fatty liver disease (NAFLD). The overexpression of hepatic miR-34a lowered insulin signaling and altered glucose metabolism in hepatocytes. In contrast, reducing miR-34a expression significantly reversed hepatic IR indices induced by palmitic acid (PA)/HFD. ENO3 was identified as a direct target gene of miR-34a. Overexpression of ENO3 effectively inhibited high-fat-induced hepatic IR-related indices both in vitro and in vivo. Moreover, the expression patterns of members of the miR-34a/ENO3 pathway in the liver tissues of NAFLD patients was in line with the findings of both cellular and animal studies. A high-fat-induced increase in hepatic miR-34a levels attenuates insulin signaling and impairs glucose metabolism by suppressing the expression of its target gene ENO3, ultimately leading to hepatic IR. The miR-34a/ENO3 pathway may be a potential therapeutic target for hepatic IR and related metabolic diseases. MDPI 2023-10-31 /pmc/articles/PMC10650923/ /pubmed/37960269 http://dx.doi.org/10.3390/nu15214616 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Yuanyuan
Zhao, Xue
Zhang, Liuchao
Yang, Chunxiao
Zhang, Kening
Gu, Zhuo
Ding, Haiyan
Li, Shuangshuang
Qin, Jian
Chu, Xia
MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3
title MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3
title_full MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3
title_fullStr MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3
title_full_unstemmed MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3
title_short MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3
title_sort microrna-34a mediates high-fat-induced hepatic insulin resistance by targeting eno3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650923/
https://www.ncbi.nlm.nih.gov/pubmed/37960269
http://dx.doi.org/10.3390/nu15214616
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