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Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway

Zinc is an essential trace element that is often reduced under the type 1 diabetic condition. Previous studies demonstrated that zinc deficiency enhanced type 1 diabetes-induced liver injury and that zinc supplementation significantly helped to prevent this. Due to the differences in pathogenesis be...

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Autores principales: Yu, Lechu, Liu, Yuanyuan, Jin, Yichun, Liu, Tinghao, Wang, Wenhan, Lu, Xuemian, Zhang, Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279848/
https://www.ncbi.nlm.nih.gov/pubmed/34307690
http://dx.doi.org/10.1155/2021/6662418
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author Yu, Lechu
Liu, Yuanyuan
Jin, Yichun
Liu, Tinghao
Wang, Wenhan
Lu, Xuemian
Zhang, Chi
author_facet Yu, Lechu
Liu, Yuanyuan
Jin, Yichun
Liu, Tinghao
Wang, Wenhan
Lu, Xuemian
Zhang, Chi
author_sort Yu, Lechu
collection PubMed
description Zinc is an essential trace element that is often reduced under the type 1 diabetic condition. Previous studies demonstrated that zinc deficiency enhanced type 1 diabetes-induced liver injury and that zinc supplementation significantly helped to prevent this. Due to the differences in pathogenesis between type 1 and type 2 diabetes, it is unknown whether zinc supplementation can induce a beneficial effect on type 2 diabetes-induced liver injury. This possible protective mechanism was investigated in the present study. A high-fat diet, along with a one-time dose of streptozotocin, was applied to metallothionein (MT) knockout mice, nuclear factor-erythroid 2-related factor (Nrf) 2 knockout mice, and age-matched wild-type (WT) control mice, in order to induce type 2 diabetes. This was followed by zinc treatment at 5 mg/kg body weight given every other day for 3 months. Global metabolic disorders of both glucose and lipids were unaffected by zinc supplementation. This induced preventive effects on conditions caused by type 2 diabetes like oxidative stress, apoptosis, the subsequent hepatic inflammatory response, fibrosis, hypertrophy, and hepatic dysfunction. Additionally, we also observed that type 2 diabetes reduced hepatic MT expression, while zinc supplementation induced hepatic MT expression. This is a crucial antioxidant. A mechanistic study showed that MT deficiency blocked zinc supplementation-induced hepatic protection under the condition of type 2 diabetes. This suggested that endogenous MT is involved in the hepatic protection of zinc supplementation in type 2 diabetic mice. Furthermore, zinc supplementation-induced hepatic MT increase was unobserved once Nrf2 was deficient, indicating that Nrf2 mediated the upregulation of hepatic MT in response to zinc supplementation. Results of this study indicated that zinc supplementation prevented type 2 diabetes-induced liver injury through the activation of the Nrf2-MT-mediated antioxidative pathway.
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spelling pubmed-82798482021-07-22 Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway Yu, Lechu Liu, Yuanyuan Jin, Yichun Liu, Tinghao Wang, Wenhan Lu, Xuemian Zhang, Chi J Diabetes Res Research Article Zinc is an essential trace element that is often reduced under the type 1 diabetic condition. Previous studies demonstrated that zinc deficiency enhanced type 1 diabetes-induced liver injury and that zinc supplementation significantly helped to prevent this. Due to the differences in pathogenesis between type 1 and type 2 diabetes, it is unknown whether zinc supplementation can induce a beneficial effect on type 2 diabetes-induced liver injury. This possible protective mechanism was investigated in the present study. A high-fat diet, along with a one-time dose of streptozotocin, was applied to metallothionein (MT) knockout mice, nuclear factor-erythroid 2-related factor (Nrf) 2 knockout mice, and age-matched wild-type (WT) control mice, in order to induce type 2 diabetes. This was followed by zinc treatment at 5 mg/kg body weight given every other day for 3 months. Global metabolic disorders of both glucose and lipids were unaffected by zinc supplementation. This induced preventive effects on conditions caused by type 2 diabetes like oxidative stress, apoptosis, the subsequent hepatic inflammatory response, fibrosis, hypertrophy, and hepatic dysfunction. Additionally, we also observed that type 2 diabetes reduced hepatic MT expression, while zinc supplementation induced hepatic MT expression. This is a crucial antioxidant. A mechanistic study showed that MT deficiency blocked zinc supplementation-induced hepatic protection under the condition of type 2 diabetes. This suggested that endogenous MT is involved in the hepatic protection of zinc supplementation in type 2 diabetic mice. Furthermore, zinc supplementation-induced hepatic MT increase was unobserved once Nrf2 was deficient, indicating that Nrf2 mediated the upregulation of hepatic MT in response to zinc supplementation. Results of this study indicated that zinc supplementation prevented type 2 diabetes-induced liver injury through the activation of the Nrf2-MT-mediated antioxidative pathway. Hindawi 2021-07-07 /pmc/articles/PMC8279848/ /pubmed/34307690 http://dx.doi.org/10.1155/2021/6662418 Text en Copyright © 2021 Lechu Yu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yu, Lechu
Liu, Yuanyuan
Jin, Yichun
Liu, Tinghao
Wang, Wenhan
Lu, Xuemian
Zhang, Chi
Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
title Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
title_full Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
title_fullStr Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
title_full_unstemmed Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
title_short Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
title_sort zinc supplementation prevented type 2 diabetes-induced liver injury mediated by the nrf2-mt antioxidative pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279848/
https://www.ncbi.nlm.nih.gov/pubmed/34307690
http://dx.doi.org/10.1155/2021/6662418
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