Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function

Item, Flurin; Wueest, Stephan; Lemos, Vera; Stein, Sokrates; Lucchini, Fabrizio C.; Denzler, Rémy; Fisser, Muriel C.; Challa, Tenagne D.; Pirinen, Eija; Kim, Youngsoo; Hemmi, Silvio; Gulbins, Erich; Gross, Atan; O’Reilly, Lorraine A.; Stoffel, Markus; Auwerx, Johan; Konrad, Daniel

doi:10.1038/s41467-017-00566-9

Cited by 44 publications

(29 citation statements)

References 54 publications

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“…Leukemia, also known as blood cancer, is a kind of malignant tumor in the hematopoietic system. Generally, it can be divided into several types, such as acute lymphoblastic leukemia ( 46 ), acute myeloid leukemia (AML), and chronic myelocytic leukemia (CML) ( 47 ). Recent studies have demonstrated that the crude ethanolic extract of Marsdenia tenacissima (CME) exhibited strong cytotoxicity against CML cell lines K562 in vitro and in vivo , and this cytotoxicity was related to inducing cell cycle (G0/G1) arrest through upregulating cyclin D1 and cell apoptosis through upregulating pro-apoptosis proteins caspase-3, caspase-9 and Bax ( 3 ).…”

Section: Marsdenia Tenacissima Effects Against Hematologicalmentioning

confidence: 99%

The Antitumor Activities of Marsdenia tenacissima

et al. 2018

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Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization.

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Section: Marsdenia Tenacissima Effects Against Hematologicalmentioning

confidence: 99%

The Antitumor Activities of Marsdenia tenacissima

et al. 2018

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“…As the central metabolic site of lipogenesis (lipid synthesis) and fatty acid β-oxidation (lipid utilization), the liver is the dominant organ regulating the process of lipid metabolism, and disturbances in hepatic lipid metabolism, characterized as aberrant hepatic lipid accumulation, are closely linked to various metabolic and cardiovascular diseases, including metabolic syndrome, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. 13,14 It is well known that hepatocytes are crucial cells involved in hepatic lipid metabolism. Fatty acids are synthesized in hepatocytes and then converted into triglycerides and finally exported into the blood circulation.…”

Section: Introductionmentioning

confidence: 99%

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

Duan¹,

Liang²,

Lin³

et al. 2018

IJN

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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.

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“…Kim et al (1996) revealed HBV may play a key role in the process of chronic hepatitis B by activating the expression of IGF1R, leading to liver fibrosis and progressing into HCC. FAS functions to modulate hepatic mitochondrial metabolism and fatty acid oxidation contributing to nonalcoholic fatty liver disease, which generally develops to liver fibrosis and HCC (Cullen and Martin, 2015;Item et al, 2017). This study explains the activation of potential carcinogenic signals by immune factor receptors (Pitt et al, 2016).…”

Section: Discussionmentioning

confidence: 78%

Mining Prognostic Biomarkers of Hepatocellular Carcinoma Based on Immune-Associated Genes

Chen

Tang

et al. 2020

DNA and Cell Biology

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This research aims to investigate the immune-associated gene signature from databases to improve the prognostic value in hepatocellular carcinoma (HCC) by multidimensional methods using various bioinformatic methods. Fifty-one immune-associated genes were mined out, which were associated with clinical characters through univariate and multivariate Cox regression analyses, and 51 immune-associated genes could be welldivided HCC samples into high-risk and low-risk clusters. Next, we performed least absolute shrinkage and selection operator (LASSO) Cox regression method to reveal 18 immune-associated genes' signature and calculate risk score of each gene for receiver operating characteristic (ROC) analysis. Comparing with low-risk cluster, high-risk cluster had higher risk score with unfavorable prognosis. Then, multivariate Cox regression analysis showed that risk score of 18 immune-associated genes' signature was associated with tumor invasion and tumor-node-metastasis (TNM) stage. ROC analysis indicated combined TNM stage, and risk score performed more sensitive and specific than single TNM stage or risk score in survival prediction. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the pathways enriched in tumorigenesis were related to risk score, and those pathways could separate HCC samples into high and low clusters. In addition, the survival prediction of 18 immune-associated genes' signature was well validated in independent test data set, external data set, and Real-time Quantitative PCR (RT-qPCR) experiment. The 18 immuneassociated genes' signature was constructed, which could be used in effective prediction of HCC prognosis.

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Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function

Cited by 44 publications

References 54 publications

The Antitumor Activities of Marsdenia tenacissima

The Antitumor Activities of Marsdenia tenacissima

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

Mining Prognostic Biomarkers of Hepatocellular Carcinoma Based on Immune-Associated Genes

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