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Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice

Liver pathological changes are as high as 21%-78% in diabetic patients, and treatment options are lacking. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor that is widely used in the clinic and is approved to treat obesity and diabetes. However, the specific protection mechanism needs to be...

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Autores principales: Song, Ji-Xian, An, Ji-Ren, Chen, Qi, Yang, Xin-Yue, Jia, Cui-Ling, Xu, Shan, Zhao, Ya-shuo, Ji, En-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161873/
https://www.ncbi.nlm.nih.gov/pubmed/35311455
http://dx.doi.org/10.1080/21655979.2022.2051858
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author Song, Ji-Xian
An, Ji-Ren
Chen, Qi
Yang, Xin-Yue
Jia, Cui-Ling
Xu, Shan
Zhao, Ya-shuo
Ji, En-Sheng
author_facet Song, Ji-Xian
An, Ji-Ren
Chen, Qi
Yang, Xin-Yue
Jia, Cui-Ling
Xu, Shan
Zhao, Ya-shuo
Ji, En-Sheng
author_sort Song, Ji-Xian
collection PubMed
description Liver pathological changes are as high as 21%-78% in diabetic patients, and treatment options are lacking. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor that is widely used in the clinic and is approved to treat obesity and diabetes. However, the specific protection mechanism needs to be clarified. In the present study, db/db mice were used to simulate Type 2 diabetes mellitus (T2DM), and they were intraperitoneally injected daily with liraglutide (200 μg/kg/d) for 5 weeks. Hepatic function, pathologic changes, oxidative stress, iron levels, and ferroptosis were evaluated. First, liraglutide decreased serum AST and ALT levels, and suppressed liver fibrosis in db/db mice. Second, liraglutide inhibited the ROS production by upregulating SOD, GSH-PX, and GSH activity as well as by downregulating MDA, 4-HNE, and NOX4 expression in db/db mice. Furthermore, liraglutide attenuated iron deposition by decreasing TfR1 expression and increasing FPN1 expression. At the same time, liraglutide decreased ferroptosis by elevating the expression of SLC7A11 and the Nrf2/HO-1/GPX4 signaling pathway in the livers of db/db mice. In addition, liraglutide decreased the high level of labile iron pools (LIPs) and intracellular lipid ROS induced by high glucose in vitro. Therefore, we speculated that liraglutide played a crucial role in reducing iron accumulation, oxidative damage and ferroptosis in db/db mice.
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spelling pubmed-91618732022-06-03 Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice Song, Ji-Xian An, Ji-Ren Chen, Qi Yang, Xin-Yue Jia, Cui-Ling Xu, Shan Zhao, Ya-shuo Ji, En-Sheng Bioengineered Research Paper Liver pathological changes are as high as 21%-78% in diabetic patients, and treatment options are lacking. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor that is widely used in the clinic and is approved to treat obesity and diabetes. However, the specific protection mechanism needs to be clarified. In the present study, db/db mice were used to simulate Type 2 diabetes mellitus (T2DM), and they were intraperitoneally injected daily with liraglutide (200 μg/kg/d) for 5 weeks. Hepatic function, pathologic changes, oxidative stress, iron levels, and ferroptosis were evaluated. First, liraglutide decreased serum AST and ALT levels, and suppressed liver fibrosis in db/db mice. Second, liraglutide inhibited the ROS production by upregulating SOD, GSH-PX, and GSH activity as well as by downregulating MDA, 4-HNE, and NOX4 expression in db/db mice. Furthermore, liraglutide attenuated iron deposition by decreasing TfR1 expression and increasing FPN1 expression. At the same time, liraglutide decreased ferroptosis by elevating the expression of SLC7A11 and the Nrf2/HO-1/GPX4 signaling pathway in the livers of db/db mice. In addition, liraglutide decreased the high level of labile iron pools (LIPs) and intracellular lipid ROS induced by high glucose in vitro. Therefore, we speculated that liraglutide played a crucial role in reducing iron accumulation, oxidative damage and ferroptosis in db/db mice. Taylor & Francis 2022-03-21 /pmc/articles/PMC9161873/ /pubmed/35311455 http://dx.doi.org/10.1080/21655979.2022.2051858 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Song, Ji-Xian
An, Ji-Ren
Chen, Qi
Yang, Xin-Yue
Jia, Cui-Ling
Xu, Shan
Zhao, Ya-shuo
Ji, En-Sheng
Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
title Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
title_full Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
title_fullStr Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
title_full_unstemmed Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
title_short Liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
title_sort liraglutide attenuates hepatic iron levels and ferroptosis in db/db mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161873/
https://www.ncbi.nlm.nih.gov/pubmed/35311455
http://dx.doi.org/10.1080/21655979.2022.2051858
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