Journal: The Journal of Biological Chemistry
Article Title: Covalent binding of thioredoxin to TXNIP is required for diet-induced insulin resistance in the liver
doi: 10.1016/j.jbc.2025.110214
Figure Lengend Snippet: A single amino acid mutation in TXNIP protein alters cholesterol pathway and insulin signaling genes in mouse livers. A , KEGG pathway analysis of WT, TXNIP C247S, and TXNIP KO groups’ liver gene expression fold-change comparisons (log2-fold expression) from bulk RNA-Seq experiments (n = 5, significance was determined as FDR ≤ 0.1). B , cholesterol biosynthesis pathway (upregulated genes in C247S mice livers are highlighted in yellow ), created with BioRender, ( C ) qPCR validation of upregulated cholesterol biosynthesis pathway genes in a different cohort of mouse livers (n = 6). Liver mRNA expressions of ( D ) Tm7sf2 and ( E ) Irs2 in HFD-fed WT, TXNIP C247S, and TXNIP KO mice that are on HFD for 8 weeks (n = 10). F , liver mRNA expressions of Irs1 in HFD-fed WT, TXNIP C247S, and TXNIP KO mice that are on HFD for 8 weeks (n = 6). Liver mRNA expressions of ( G ) Tm7sf2 and ( H ) Irs2 in chow-fed WT, TXNIP C247S, and TXNIP KO mice (n = 6). I , liver mRNA expressions of Pck1 in HFD-fed WT and TXNIP C247S mice that are on HFD for 8 weeks (n = 6). Data represented as mean ± standard deviation, one-way ANOVA with Tukey post hoc tests were used, ∗ p < 0.05, ∗∗ p < 0.005, ∗∗∗ p < 0005, and ∗∗∗∗ p < 0.00005. C247S, Cysteine 247 for Serine; FDR, false discovery rate; KEGG, Kyoto Encyclopedia of Genes and Genomes; qPCR, quantitative PCR; TXNIP, Thioredoxin-Interacting Protein.
Article Snippet: Cells were transfected with EV or Tm7sf2 vector (NET47 pEGFP-N2 [593] was a gift from Eric Schirmer, Addgene plasmid #61986) using Lipofectamine 3000 reagent (Thermo Fisher).
Techniques: Mutagenesis, Gene Expression, Expressing, RNA Sequencing, Biomarker Discovery, Standard Deviation, Real-time Polymerase Chain Reaction