PUBLICATION
Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro
- Authors
- Duan, J., Liang, S., Feng, L., Yu, Y., Sun, Z.
- ID
- ZDB-PUB-181207-23
- Date
- 2018
- Source
- International Journal of Nanomedicine 13: 7303-7318 (Journal)
- Registered Authors
- Keywords
- TLR5-signaling pathway, hepatic lipid metabolism, hepatic steatosis, hyperlipemia, silica nanoparticles
- Datasets
- GEO:GSE73427
- MeSH Terms
-
- Animals
- Biomarkers/metabolism
- Cell Death
- Cell Line
- Diet, High-Fat
- Fatty Liver/blood
- Fatty Liver/drug therapy
- Fatty Liver/pathology
- Hepatocytes/metabolism
- Humans
- Inflammation/pathology
- Lipid Metabolism*
- Lipids/blood
- Liver/drug effects
- Liver/metabolism*
- Liver/pathology*
- Liver/ultrastructure
- Male
- Mice, Inbred ICR
- Models, Biological
- Nanoparticles/toxicity*
- Nanoparticles/ultrastructure
- Silicon Dioxide/toxicity*
- Toll-Like Receptor 5/metabolism
- Tumor Necrosis Factor-alpha/metabolism
- Zebrafish
- PubMed
- 30519016 Full text @ Int. J. Nanomedicine
Citation
Duan, J., Liang, S., Feng, L., Yu, Y., Sun, Z. (2018) Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro. International Journal of Nanomedicine. 13:7303-7318.
Abstract
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.
Genes / Markers
Expression
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping