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High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling
High fat diet could cause kidney injury, and the underlying mechanism remains incompletely understood. In this study, we investigated the role of Wnt signaling in this process. Mice were fed with high-fat diet in vivo, and podocytes were stimulated with palmitate in vitro. In mice fed with high-fat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021428/ https://www.ncbi.nlm.nih.gov/pubmed/35462998 http://dx.doi.org/10.3389/fmed.2022.851618 |
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author | Yu, Ying Mo, Hongyan Zhuo, Hui Yu, Chen Liu, Youhua |
author_facet | Yu, Ying Mo, Hongyan Zhuo, Hui Yu, Chen Liu, Youhua |
author_sort | Yu, Ying |
collection | PubMed |
description | High fat diet could cause kidney injury, and the underlying mechanism remains incompletely understood. In this study, we investigated the role of Wnt signaling in this process. Mice were fed with high-fat diet in vivo, and podocytes were stimulated with palmitate in vitro. In mice fed with high-fat diet, renal function was impaired, accompanied by induction of various proinflammatory cytokines and proteinuria. Renal expression of Wnt ligands was also significantly induced, with Wnt1 and Wnt3a being the most pronounced, in high-fat diet mice, compared with normal diet controls. Intervention with ICG-001, a small molecule Wnt/β-catenin inhibitor, improved renal function, inhibited proinflammatory cytokines expression, reduced proteinuria and alleviated podocyte injury. In palmitate-treated podocytes, intracellular lipid deposition was increased, Wnt1 and Wnt3a expression was up-regulated, which was accompanied by an increased proinflammatory cytokines expression and podocyte injury. These lesions caused by palmitate were largely alleviated by ICG-001. Furthermore, ICG-001 also restored the expression of phosphorylated AMPK repressed by palmitate in podocytes or a high-fat diet in mice. These studies suggest that Wnt/β-catenin signaling is involved in the pathogenesis of high-fat diet-induced kidney injury. Targeting this signaling may be a potential therapeutic strategy for alleviating obesity-related nephropathy. |
format | Online Article Text |
id | pubmed-9021428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90214282022-04-22 High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling Yu, Ying Mo, Hongyan Zhuo, Hui Yu, Chen Liu, Youhua Front Med (Lausanne) Medicine High fat diet could cause kidney injury, and the underlying mechanism remains incompletely understood. In this study, we investigated the role of Wnt signaling in this process. Mice were fed with high-fat diet in vivo, and podocytes were stimulated with palmitate in vitro. In mice fed with high-fat diet, renal function was impaired, accompanied by induction of various proinflammatory cytokines and proteinuria. Renal expression of Wnt ligands was also significantly induced, with Wnt1 and Wnt3a being the most pronounced, in high-fat diet mice, compared with normal diet controls. Intervention with ICG-001, a small molecule Wnt/β-catenin inhibitor, improved renal function, inhibited proinflammatory cytokines expression, reduced proteinuria and alleviated podocyte injury. In palmitate-treated podocytes, intracellular lipid deposition was increased, Wnt1 and Wnt3a expression was up-regulated, which was accompanied by an increased proinflammatory cytokines expression and podocyte injury. These lesions caused by palmitate were largely alleviated by ICG-001. Furthermore, ICG-001 also restored the expression of phosphorylated AMPK repressed by palmitate in podocytes or a high-fat diet in mice. These studies suggest that Wnt/β-catenin signaling is involved in the pathogenesis of high-fat diet-induced kidney injury. Targeting this signaling may be a potential therapeutic strategy for alleviating obesity-related nephropathy. Frontiers Media S.A. 2022-04-07 /pmc/articles/PMC9021428/ /pubmed/35462998 http://dx.doi.org/10.3389/fmed.2022.851618 Text en Copyright © 2022 Yu, Mo, Zhuo, Yu and Liu. 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 | Medicine Yu, Ying Mo, Hongyan Zhuo, Hui Yu, Chen Liu, Youhua High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling |
title | High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling |
title_full | High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling |
title_fullStr | High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling |
title_full_unstemmed | High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling |
title_short | High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling |
title_sort | high fat diet induces kidney injury via stimulating wnt/β-catenin signaling |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021428/ https://www.ncbi.nlm.nih.gov/pubmed/35462998 http://dx.doi.org/10.3389/fmed.2022.851618 |
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