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Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis

Empagliflozin (EMPA) is a novel sodium-glucose cotransporter 2 inhibitor (SGLT2i) that produces protective cardiovascular-renal outcomes in patients with diabetes. However, the effects of EMPA on obesity-related kidney disease have not been determined. The heme oxygenase-1 (HO-1)–adiponectin axis is...

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Autores principales: Ye, Tongtong, Zhang, Jingwen, Wu, Di, Shi, Junfeng, Kuang, Zengguang, Ma, Yuting, Xu, Qian, Chen, Bing, Kan, Chengxia, Sun, Xiaodong, Han, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248377/
https://www.ncbi.nlm.nih.gov/pubmed/35784553
http://dx.doi.org/10.3389/fendo.2022.907984
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author Ye, Tongtong
Zhang, Jingwen
Wu, Di
Shi, Junfeng
Kuang, Zengguang
Ma, Yuting
Xu, Qian
Chen, Bing
Kan, Chengxia
Sun, Xiaodong
Han, Fang
author_facet Ye, Tongtong
Zhang, Jingwen
Wu, Di
Shi, Junfeng
Kuang, Zengguang
Ma, Yuting
Xu, Qian
Chen, Bing
Kan, Chengxia
Sun, Xiaodong
Han, Fang
author_sort Ye, Tongtong
collection PubMed
description Empagliflozin (EMPA) is a novel sodium-glucose cotransporter 2 inhibitor (SGLT2i) that produces protective cardiovascular-renal outcomes in patients with diabetes. However, the effects of EMPA on obesity-related kidney disease have not been determined. The heme oxygenase-1 (HO-1)–adiponectin axis is an essential antioxidant system with anti-apoptotic and anti-inflammatory properties. This study explored whether EMPA improves obesity-related kidney disease through regulation of the renal HO-1-mediated adiponectin axis. C57BL/6J mice were assigned to control, high-fat diet (HFD) groups, and EMPA (10 mg/kg) groups. HFD mice showed metabolic abnormality and renal injury, including increased urinary albumin excretion, morphologic changes, and lipid accumulation. EMPA treatment improved metabolic disorders and attenuated lipotoxicity-induced renal injury. Furthermore, EMPA treatment ameliorated renal NLRP3 inflammasome activity and upregulated the HO-1–adiponectin axis. Our findings indicate that EMPA improves obesity-related kidney disease through reduction of NLRP3 inflammasome activity and upregulation of the HO-1–adiponectin axis, suggesting a novel mechanism for SGLT2i-mediated renal protection in obesity.
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spelling pubmed-92483772022-07-02 Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis Ye, Tongtong Zhang, Jingwen Wu, Di Shi, Junfeng Kuang, Zengguang Ma, Yuting Xu, Qian Chen, Bing Kan, Chengxia Sun, Xiaodong Han, Fang Front Endocrinol (Lausanne) Endocrinology Empagliflozin (EMPA) is a novel sodium-glucose cotransporter 2 inhibitor (SGLT2i) that produces protective cardiovascular-renal outcomes in patients with diabetes. However, the effects of EMPA on obesity-related kidney disease have not been determined. The heme oxygenase-1 (HO-1)–adiponectin axis is an essential antioxidant system with anti-apoptotic and anti-inflammatory properties. This study explored whether EMPA improves obesity-related kidney disease through regulation of the renal HO-1-mediated adiponectin axis. C57BL/6J mice were assigned to control, high-fat diet (HFD) groups, and EMPA (10 mg/kg) groups. HFD mice showed metabolic abnormality and renal injury, including increased urinary albumin excretion, morphologic changes, and lipid accumulation. EMPA treatment improved metabolic disorders and attenuated lipotoxicity-induced renal injury. Furthermore, EMPA treatment ameliorated renal NLRP3 inflammasome activity and upregulated the HO-1–adiponectin axis. Our findings indicate that EMPA improves obesity-related kidney disease through reduction of NLRP3 inflammasome activity and upregulation of the HO-1–adiponectin axis, suggesting a novel mechanism for SGLT2i-mediated renal protection in obesity. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9248377/ /pubmed/35784553 http://dx.doi.org/10.3389/fendo.2022.907984 Text en Copyright © 2022 Ye, Zhang, Wu, Shi, Kuang, Ma, Xu, Chen, Kan, Sun and Han 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 Endocrinology
Ye, Tongtong
Zhang, Jingwen
Wu, Di
Shi, Junfeng
Kuang, Zengguang
Ma, Yuting
Xu, Qian
Chen, Bing
Kan, Chengxia
Sun, Xiaodong
Han, Fang
Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis
title Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis
title_full Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis
title_fullStr Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis
title_full_unstemmed Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis
title_short Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1–Adiponectin Axis
title_sort empagliflozin attenuates obesity-related kidney dysfunction and nlrp3 inflammasome activity through the ho-1–adiponectin axis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248377/
https://www.ncbi.nlm.nih.gov/pubmed/35784553
http://dx.doi.org/10.3389/fendo.2022.907984
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