Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

Junchao Duan,1,2 Shuang Liang,1,2 Lin Feng,1,2 Yang Yu,1,2 Zhiwei Sun1,2 1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China Back...

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Autores principales:	Duan J, Liang S, Feng L, Yu Y, Sun Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Silica nanoparticles hyperlipemia hepatic steatosis hepatic lipid metabolism TLR5 signaling pathway Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/481a357f56664a139a95847c4627c26b
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spelling	oai:doaj.org-article:481a357f56664a139a95847c4627c26b2021-12-02T00:13:13ZSilica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro1178-2013https://doaj.org/article/481a357f56664a139a95847c4627c26b2018-11-01T00:00:00Zhttps://www.dovepress.com/silica-nanoparticles-trigger-hepatic-lipid-metabolism-disorder-in-vivo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Junchao Duan,1,2 Shuang Liang,1,2 Lin Feng,1,2 Yang Yu,1,2 Zhiwei Sun1,2 1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China Background: As a promising nanocarrier in biomedical fields, silica nanoparticles (SiNPs) could transfer from the circulatory system to multiple organs. Among these, blood–liver molecular exchange is a critical factor in biological response to NPs. However, the potential effect of SiNPs on hepatic lipid metabolism is unclear. In this study, we employed three models to attempt discover whether and how SiNPs disturb hepatic lipid metabolism in vivo and in vitro. Methods: Firstly we used ICR mice models to evaulated the effects of SiNPs on the serum and hepatic lipid levels through repeated intravenous administration, meanwhile, the protein expressions of protein markers of lipogenesis (ACC1 and FAS ), the key enzyme of fatty acid β-oxidation, CPT1A,and leptin levels in liver were detected by western blot. For verification studies, the model organism zebrafish and cultured hepatic L02 cells were further performed. The TLR5 and adipocytokine-signaling pathway were verified. Results: Inflammatory cell infiltration and mild steatosis induced by SiNPs were observed in the liver. Cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were elevated significantly in both blood serum and liver tissue, whereas the ratio of high-density:low-density lipoprotein cholesterol was markedly decreased. Protein markers of lipogenesis (ACC1 and FAS) were elevated significantly in liver tissue, whereas the key enzyme of fatty acid β-oxidation, CPT1A, was decreased significantly. Interestingly, leptin levels in the SiNP-treated group were also elevated markedly. In addition, SiNPs caused hepatic damage and steatosis in zebrafish and enhanced hyperlipemia in high-cholesterol diet zebrafish. Similarly, SiNPs increased the release of inflammatory cytokines (IL1β, IL6, IL8, and TNFα) and activated the TLR5-signaling pathway in hepatic L02 cells. Conclusion: In summary, our study found that SiNPs triggered hyperlipemia and hepatic steatosis via the TLR5-signaling pathway. This suggests that regulation of TLR5 could be a novel therapeutic target to reduce side effects of NPs in living organisms. Keywords: silica nanoparticles, hyperlipemia, hepatic steatosis, hepatic lipid metabolism, TLR5-signaling pathwayDuan JLiang SFeng LYu YSun ZDove Medical PressarticleSilica nanoparticleshyperlipemiahepatic steatosishepatic lipid metabolismTLR5 signaling pathwayMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7303-7318 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Silica nanoparticles hyperlipemia hepatic steatosis hepatic lipid metabolism TLR5 signaling pathway Medicine (General) R5-920
spellingShingle	Silica nanoparticles hyperlipemia hepatic steatosis hepatic lipid metabolism TLR5 signaling pathway Medicine (General) R5-920 Duan J Liang S Feng L Yu Y Sun Z Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
description	Junchao Duan,1,2 Shuang Liang,1,2 Lin Feng,1,2 Yang Yu,1,2 Zhiwei Sun1,2 1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China Background: As a promising nanocarrier in biomedical fields, silica nanoparticles (SiNPs) could transfer from the circulatory system to multiple organs. Among these, blood–liver molecular exchange is a critical factor in biological response to NPs. However, the potential effect of SiNPs on hepatic lipid metabolism is unclear. In this study, we employed three models to attempt discover whether and how SiNPs disturb hepatic lipid metabolism in vivo and in vitro. Methods: Firstly we used ICR mice models to evaulated the effects of SiNPs on the serum and hepatic lipid levels through repeated intravenous administration, meanwhile, the protein expressions of protein markers of lipogenesis (ACC1 and FAS ), the key enzyme of fatty acid β-oxidation, CPT1A,and leptin levels in liver were detected by western blot. For verification studies, the model organism zebrafish and cultured hepatic L02 cells were further performed. The TLR5 and adipocytokine-signaling pathway were verified. Results: Inflammatory cell infiltration and mild steatosis induced by SiNPs were observed in the liver. Cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were elevated significantly in both blood serum and liver tissue, whereas the ratio of high-density:low-density lipoprotein cholesterol was markedly decreased. Protein markers of lipogenesis (ACC1 and FAS) were elevated significantly in liver tissue, whereas the key enzyme of fatty acid β-oxidation, CPT1A, was decreased significantly. Interestingly, leptin levels in the SiNP-treated group were also elevated markedly. In addition, SiNPs caused hepatic damage and steatosis in zebrafish and enhanced hyperlipemia in high-cholesterol diet zebrafish. Similarly, SiNPs increased the release of inflammatory cytokines (IL1β, IL6, IL8, and TNFα) and activated the TLR5-signaling pathway in hepatic L02 cells. Conclusion: In summary, our study found that SiNPs triggered hyperlipemia and hepatic steatosis via the TLR5-signaling pathway. This suggests that regulation of TLR5 could be a novel therapeutic target to reduce side effects of NPs in living organisms. Keywords: silica nanoparticles, hyperlipemia, hepatic steatosis, hepatic lipid metabolism, TLR5-signaling pathway
format	article
author	Duan J Liang S Feng L Yu Y Sun Z
author_facet	Duan J Liang S Feng L Yu Y Sun Z
author_sort	Duan J
title	Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
title_short	Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
title_full	Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
title_fullStr	Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
title_full_unstemmed	Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
title_sort	silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/481a357f56664a139a95847c4627c26b
work_keys_str_mv	AT duanj silicananoparticlestriggerhepaticlipidmetabolismdisorderinvivoandinvitro AT liangs silicananoparticlestriggerhepaticlipidmetabolismdisorderinvivoandinvitro AT fengl silicananoparticlestriggerhepaticlipidmetabolismdisorderinvivoandinvitro AT yuy silicananoparticlestriggerhepaticlipidmetabolismdisorderinvivoandinvitro AT sunz silicananoparticlestriggerhepaticlipidmetabolismdisorderinvivoandinvitro
_version_	1718403862466920448

Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

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