3,5-T2 alters murine genes relevant for xenobiotic, steroid, and thyroid hormone metabolism
- 1Institut für Experimentelle Endokrinologie, Charité – Universitätsmedizin Berlin, Berlin, Germany
- 2Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany
- 3Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- 4German Center for Diabetes Research (DZD), Helmholtz Center Munich, Neuherberg, Germany
- Correspondence should be addressed to J Köhrle; Email: josef.koehrle{at}charite.de
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Figure 3
Expression of TH responsive genes after 3,5-T2 treatment: hepatic mRNA levels of Dio1 encoding deiodinase 1 (A) and Serpina7 encoding thyroxine-binding globulin (B) were assayed by RT-qPCR using RNA samples prepared from livers of mice fed high-fat diet (HFD) or normal diet (ND) treated with 3,5-T2 or saline as control. Corresponding significant fold changes of gene expression in liver of 3,5-T2-treated HFD or ND mice determined by microarray-based transcriptome analysis were added to the graph. Data are expressed as mean ± s.e.m. Mann–Whitney U test was used for statistical comparisons of RT-qPCR data. Significantly different as compared with the saline group: *P<0.05, **P<0.01, ***P<0.001.
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Figure 4
The influence of 3,5-T2 treatment on the expression of genes encoding drug-metabolizing enzymes (DME). Genes differentially expressed after 3,5-T2 treatment for 2 and 4 weeks in mice fed high-fat diet (HFD) or for 4 weeks in mice fed normal diet (ND) are shown. Gene products were classified in drug-metabolizing enzymes (DME) including Phase I and Phase II enzymes as well as Phase III transporters. The heat map on the right-hand side shows significantly differentially expressed genes (*P<0.05) compared with the corresponding control groups (ND or HFD control) after 3,5-T2 treatment (n = 3 per group). Each cell in the heat map indicates the expression level of the corresponding gene for one animal. The highest expression levels are given in black, the lowest in white.
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Figure 5
Differential expression of genes encoding proteins involved in hepatic xenobiotic metabolism after 3,5-T2 treatment. In particular, the hepatic mRNA levels of genes encoding Phase I enzymes (A), Phase II enzymes (B), and Phase III transporters (C) were assayed by RT-qPCR using RNA prepared from livers of mice fed high-fat diet (HFD) or fed normal diet (ND) treated with 3,5-T2 or saline for 4 weeks. Corresponding significant fold changes of gene expression in liver of 3,5-T2-treated HFD or ND mice determined by microarray-based transcriptome analysis were added to the graph. Cyp: cytochrome P450, Ugt: UDP-glucuronosyltransferase, Sult: sulfotransferase, Abc: ATP-binding cassette transporter, Slc: solute carrier family. Data are expressed as mean ± s.e.m. Mann–Whitney U test was used for statistical comparisons of RT-qPCR data. Significantly different as compared with the saline group: *P<0.05, **P<0.01, ***P<0.001.
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Figure 6
Detection of 3,5-T2 concentration-dependent differential Sult1a1 expression by RT-qPCR using RNA prepared from primary hepatocytes cultured for 24 h in the absence (c) or presence of 10 nM; 100 nM, 1 µM, or 10 µM 3,5-T2. Data are expressed as mean ± s.e.m (n = 3 in triplicates). Kruskal–Wallis test (Dunn’s post-test) was used for statistical comparisons. Significantly different as compared with the control group (c): ***P<0.001.
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Figure 7
Expression of genes involved in steroid biosynthesis after 3,5-T2 treatment: hepatic mRNA levels of Sqle encoding squalene epoxidase (A) and Hsd17b7 encoding hydroxysteroid (17-β) dehydrogenase 7 (B) were determined by qPCR and by microarray based transcriptome analysis. Data are expressed as mean ± s.e.m. Mann–Whitney U test was used for statistical comparisons of RT-qPCR data. Significantly different as compared with the saline group: *P<0.05, **P<0.01, ***P<0.001.
- © 2016 Society for Endocrinology
