Nitrite induces hepatic glucose and lipid metabolism disorders in zebrafish through mitochondrial dysfunction and ERs response.

Autor: Yang H; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China., Ou-Yang K; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China., He Y; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China., Wang X; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China., Wang L; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China., Yang Q; Institute of Hydroecology, Ministry of Water Resources & Chinese Academy of Sciences, Wuhan 430079, PR China., Li D; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, PR China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China., Li L; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, PR China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China. Electronic address: foreverlili78@mail.hzau.edu.cn.
Jazyk: angličtina
Zdroj: Aquatic toxicology (Amsterdam, Netherlands) [Aquat Toxicol] 2024 Aug; Vol. 273, pp. 107015. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1016/j.aquatox.2024.107015
Abstrakt: Nitrite, a highly toxic environmental contaminant, induces various physiological toxicities in aquatic animals. Herein, we investigate the in vivo effects of nitrite exposure at concentrations of 0, 0.2, 2, and 20 mg/L on glucose and lipid metabolism in zebrafish. Our results showed that exposure to nitrite induced mitochondrial oxidative stress in zebrafish liver and ZFL cells, which were evidenced by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) as well as decreased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP). Changes in these oxidative stress markers were accompanied by alterations in the expression levels of genes involved in HIF-1α pathway (hif1α and phd), which subsequently led to the upregulation of glycolysis and gluconeogenesis-related genes (gk, pklr, pdk1, pepck, g6pca, ppp1r3cb, pgm1, gys1 and gys2), resulting in disrupted glucose metabolism. Moreover, nitrite exposure activated ERs (Endoplasmic Reticulum stress) responses through upregulating of genes (atf6, ern1 and xbp1s), leading to increased expression of lipolysis genes (pparα, cpt1aa and atgl) and decreased expression of lipid synthesis genes (srebf1, srebf2, fasn, acaca, scd, hmgcra and hmgcs1). These results were also in consistent with the observed changes in glycogen, lactate and decreased total triglyceride (TG) and total cholesterol (TC) in the liver of zebrafish. Our in vitro results showed that co-treatment with Mito-TEMPO and nitrite attenuated nitrite-induced oxidative stress and improved mitochondrial function, which were indicated by the restorations of ROS, MMP, ATP production, and glucose-related gene expression recovered. Co-treatment of TUDCA and nitrite prevented nitrite-induced ERs response and which was proved by the levels of TG and TC ameliorated as well as the expression levels of lipid metabolism-related genes. In conclusion, our study suggested that nitrite exposure disrupted hepatic glucose and lipid metabolism through mitochondrial dysfunction and ERs responses. These findings contribute to the understanding of the potential hepatotoxicity for aquatic animals in the presence of ambient nitrite.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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