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Differential Regulation Of Transcriptional Factors Of Selenoprotein Genes By Moderately High Dietary Concentrations Of Se And Fat In Liver And Adipose Tissue Of Wildtype And Gpx1 −/− Mice
Author(s) -
Zhao Zeping,
Zhou Jichang,
Lei Xin Gen
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.459.6
Subject(s) - adipose tissue , endocrinology , medicine , selenoprotein , gpx1 , myod , biology , messenger rna , chemistry , gene , glutathione peroxidase , oxidative stress , biochemistry , catalase , skeletal muscle , myogenesis
Our previous research demonstrated striking differences in regulations of selenoprotein gene mRNA between in the liver and adipose tissue of wild‐type (WT) and Gpx1 −/− male mice (2–4 months of age) by moderately high dietary concentrations of Se (1.0 vs. 0.3 mg/kg as selenite) and/or high fat (25 vs. 5% as lard). This study was followed up to explore if there was an underlying transcriptional mechanism for those differential regulations. Initially, we submitted the promoter region sequences (−2000bp to 0bp) of all the affected selenoprotein genes by the high fat and Se diets to TRANSFAC database and identified 7 common transcription factors (TF): C/ebpβ, Yy1, Hoxa5, Gr, Hes1, Nf1 and Myod . Subsequently, we determined responses of mRNA abundances of these TF to the high fat and Se diets in the liver and adipose tissue samples collected from the previous experiment (total = 40 mice, n = 5/diet by age and genotype). In the adipose tissue of the WT mice, mRNA levels of all 7 TF were consistently down‐regulated (P < 0.05) by the high Se and fat diets. In contrast, the high fat diet enhanced (P < 0.05) Myod and Hes1 and suppressed (P < 0.05) only Hoxa5 and Nf1 mRNA, while the high Se diet enhanced (P < 0.05) only C/ebpβ and Gr mRNA in the liver of WT mice. Knockout of Gpx1 allowed both positive and negative effects (P < 0.05) of the high Se and fat diets on the mRNA levels of these TF in the liver and adipose tissue, but the overall regulation seemed to be intensified in the liver and attenuated in the adipose tissue compared with those in the WT mice. Correlation analysis revealed strong positive relationships (R 2 > 0.8, P < 0.05) between mRNA of each of the 7 TF with 9 selenoproteins ( Gpx4, Gpx6, Selh, Seli, Selk, Selm, Selo, SELP, Sels and Selv ) in the adipose of WT mice. However, such correlations were shown between only 5 selenoprotein genes ( Dio2, Dio3 , GPX3, Gpx6 and Sep15 ) and 3 TF ( Myod, Hes1 and Gr ) in the liver of WT mice. Likewise, knockout of Gpx1 removed many of these correlations in the liver or adipose tissue and rendered 3 negative correlations (P < 0.05) between Gr and Dio1 and between Nf1/Yy1 and Gpx 4 in the adipose tissue. In conclusion, the differential regulations of selenoprotein gene expression in the two tissues of two genotypes by the moderately high dietary intakes of Se and fat might be mediated by their impacts on the expression of the TF having binding domains in the promoters of these genes. Support or Funding Information NIH DK 53018.