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The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy
Background: Obesity has become a worldwide epidemic, and the incidence of obesity is increasing year by year. Obesity-related nephropathy (ORN) is a common kidney complication of obesity. Long-chain acyl-CoA synthetases-1, (ACSL1), is a key enzyme in the oxidative metabolism of fatty acids in mitoch...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735294/ https://www.ncbi.nlm.nih.gov/pubmed/31488013 http://dx.doi.org/10.1080/0886022X.2019.1655450 |
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author | Chen, Yinyin He, Liyu Yang, Yiya Chen, Ying Song, Yanran Lu, Xi Liang, Yumei |
author_facet | Chen, Yinyin He, Liyu Yang, Yiya Chen, Ying Song, Yanran Lu, Xi Liang, Yumei |
author_sort | Chen, Yinyin |
collection | PubMed |
description | Background: Obesity has become a worldwide epidemic, and the incidence of obesity is increasing year by year. Obesity-related nephropathy (ORN) is a common kidney complication of obesity. Long-chain acyl-CoA synthetases-1, (ACSL1), is a key enzyme in the oxidative metabolism of fatty acids in mitochondria and ACSL1 may play a direct role in renal lipid deposition and promote the progress of ORN. In this study, we focus on the renoprotective role of ACSL1 in ORN. Methods: Electron microscopy, immunohistochemical (IHC) staining, Western blot, and real-time PCR were used to detect the expression of ACSL1and Nrf2 in ORN patients, ob/ob mice and palmitic acid (PA)-treated HK-2 cells. Oil red staining and Elisa Kit were used to detect the intracellular FFA and TG contents in ob/ob mice and PA-treated HK-2 cells. Dihydroethidium (DHE) staining and the MDA/SOD measurement were used to detect the ROS production. In order to demonstrate the role of ACSL1 and the interaction between ACSL1 and Nrf2 in ORN, related siRNA and plasmid were transfected into HK-2 cells. Results: More ROS production and renal lipid deposition have been found in ORN patients, ob/ob mice and PA-treated HK-2 cells. Compared with control, all the expression of ACSL1and Nrf2 were down-regulated in ORN patients, ob/ob mice and PA-treated HK-2 cells. The Nrf2 could regulate the expression of ACSL1 and the ACSL1 played the direct role in renal lipid deposition. Conclusions: The Nrf2 is inhibited in ORN, resulting more ROS production and oxidative stress. Increased oxidative stress will suppress the expression of ACSL1, which could increase the intracellular FFA and TG contents, ultimately leading to renal lipid deposition in renal tubulars and accelerating the development of ORN. |
format | Online Article Text |
id | pubmed-6735294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-67352942019-09-16 The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy Chen, Yinyin He, Liyu Yang, Yiya Chen, Ying Song, Yanran Lu, Xi Liang, Yumei Ren Fail Laboratory Study Background: Obesity has become a worldwide epidemic, and the incidence of obesity is increasing year by year. Obesity-related nephropathy (ORN) is a common kidney complication of obesity. Long-chain acyl-CoA synthetases-1, (ACSL1), is a key enzyme in the oxidative metabolism of fatty acids in mitochondria and ACSL1 may play a direct role in renal lipid deposition and promote the progress of ORN. In this study, we focus on the renoprotective role of ACSL1 in ORN. Methods: Electron microscopy, immunohistochemical (IHC) staining, Western blot, and real-time PCR were used to detect the expression of ACSL1and Nrf2 in ORN patients, ob/ob mice and palmitic acid (PA)-treated HK-2 cells. Oil red staining and Elisa Kit were used to detect the intracellular FFA and TG contents in ob/ob mice and PA-treated HK-2 cells. Dihydroethidium (DHE) staining and the MDA/SOD measurement were used to detect the ROS production. In order to demonstrate the role of ACSL1 and the interaction between ACSL1 and Nrf2 in ORN, related siRNA and plasmid were transfected into HK-2 cells. Results: More ROS production and renal lipid deposition have been found in ORN patients, ob/ob mice and PA-treated HK-2 cells. Compared with control, all the expression of ACSL1and Nrf2 were down-regulated in ORN patients, ob/ob mice and PA-treated HK-2 cells. The Nrf2 could regulate the expression of ACSL1 and the ACSL1 played the direct role in renal lipid deposition. Conclusions: The Nrf2 is inhibited in ORN, resulting more ROS production and oxidative stress. Increased oxidative stress will suppress the expression of ACSL1, which could increase the intracellular FFA and TG contents, ultimately leading to renal lipid deposition in renal tubulars and accelerating the development of ORN. Taylor & Francis 2019-09-05 /pmc/articles/PMC6735294/ /pubmed/31488013 http://dx.doi.org/10.1080/0886022X.2019.1655450 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://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/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Laboratory Study Chen, Yinyin He, Liyu Yang, Yiya Chen, Ying Song, Yanran Lu, Xi Liang, Yumei The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy |
title | The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy |
title_full | The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy |
title_fullStr | The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy |
title_full_unstemmed | The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy |
title_short | The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy |
title_sort | inhibition of nrf2 accelerates renal lipid deposition through suppressing the acsl1 expression in obesity-related nephropathy |
topic | Laboratory Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735294/ https://www.ncbi.nlm.nih.gov/pubmed/31488013 http://dx.doi.org/10.1080/0886022X.2019.1655450 |
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