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Antioxidant hepatic lipid metabolism can be promoted by orally administered inorganic nanoparticles.

ABSTRACT: Accumulation of inorganic nanoparticles in living organisms can cause an increase in cellular reactive oxygen species (ROS) in a dose-dependent manner. Low doses of nanoparticles have shown possibilities to induce moderate ROS increases and lead to adaptive responses of biological systems, but beneficial effects of such responses on metabolic health remain elusive. Here, we report that repeated oral administrations of various inorganic nanoparticles, including TiO₂, Au, and NaYF₄ nanoparticles at low doses, can promote lipid degradation and alleviate steatosis in the liver of male mice. We show that low-level uptake of nanoparticles evokes an unusual antioxidant response in hepatocytes by promoting Ces2h expression and consequently enhancing ester hydrolysis. This process can be implemented to treat specific hepatic metabolic disorders, such as fatty liver in both genetic and high-fat-diet obese mice without causing observed adverse effects. Our results demonstrate that low-dose nanoparticle administration may serve as a promising treatment for metabolic regulation.

SUBMITTER: Cai J

PROVIDER: S-EPMC10281969 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Antioxidant hepatic lipid metabolism can be promoted by orally administered inorganic nanoparticles.

Cai Jie J Peng Jie J Feng Juan J Li Ruocheng R Ren Peng P Zang Xinwei X Wu Zezong Z Lu Yi Y Luo Lin L Hu Zhenzhen Z Wang Jiaying J Dai Xiaomeng X Zhao Peng P Wang Juan J Yan Mi M Liu Jianxin J Deng Renren R Wang Diming D

Nature communications 20230620 1

Accumulation of inorganic nanoparticles in living organisms can cause an increase in cellular reactive oxygen species (ROS) in a dose-dependent manner. Low doses of nanoparticles have shown possibilities to induce moderate ROS increases and lead to adaptive responses of biological systems, but beneficial effects of such responses on metabolic health remain elusive. Here, we report that repeated oral administrations of various inorganic nanoparticles, including TiO<sub>2</sub>, Au, and NaYF<sub>4 ...[more]

PMID: 37339977

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Project description:BackgroundAs 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.MethodsFirstly 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.ResultsInflammatory 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.ConclusionIn 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.

Project description:BackgroundRapid influx of energy caused by fasting/refeeding repeatedly enhances fatty acid synthesis leading to triacylglycerol accumulation and production of reactive oxygen species (ROS), increasing the risk of non-alcoholic steatohepatitis (NASH). Previous studies have reported that the ingestion of butyrate is effective at preventing hepatic disorders, which are accompanied by fat accumulation and inflammation. The aim of this study is to reveal the mechanism of action of butyrate, and thus we investigated the effects of dietary butyrate on the expressions of antioxidant enzymes in the livers of rats during refeeding following fasting.MethodsThirty-seven male rats were divided into six groups (6-7 animals per group): non-fasting, fasting, refeeding with a high sucrose diet as control for 12 or 24 h, and refeeding with a high sucrose diet containing 5% sodium butyrate (NaB) for 12 or 24 h. All groups except the non-fasting group were fasted for 72 h before refeeding. Statistical analysis was conducted among 4 refeeding groups (refeeding with the control diet for 12 or 24 h, and refeeding with a diet containing NaB for 12 or 24 h).ResultsSupplementation with NaB significantly reduced (p < 0.05) fatty acid synthase (Fas) gene expression and increased the expression of the carnitine palmitoyltransferase 1α (Cpt1a) gene, resulting in reduced triacylglycerol content in the livers of rats refed the NaB diet compared with controls at 24 h after the start of refeeding. The mRNA levels of the genes related to glutathione synthesis were significantly higher (p < 0.05) in the livers of the butyrate group than the control group. In addition, the mRNA level of Foxo3a, a transcription factor that regulates the expressions of antioxidant enzymes, was higher in the butyrate group than controls. The acetylation levels of histone H4 around the Foxo3a gene tended to be increased (p = 0.055) by refeeding with the NaB diet.ConclusionNaB supplementation in the diet for refeeding reduced the rate of lipid synthesis and stimulated fatty acid oxidation in the liver, which inhibited fat accumulation and the risk of NASH. The transcriptional regulation of Foxo3a involves histone acetylation around the gene.

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Antioxidant hepatic lipid metabolism can be promoted by orally administered inorganic nanoparticles.

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Antioxidant hepatic lipid metabolism can be promoted by orally administered inorganic nanoparticles.

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