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MolMet Figure 7: Liver transcriptome analysis in GKRP^P446>L mice on the HFHSD (HD).

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posted on 2023-04-19, 15:49 authored by Brian FordBrian Ford, Loranne AgiusLoranne Agius

A) Heat map for unsupervised clustering of P446L livers of PP and LL genotypes on regular diet (P-RD, P-HD, n=4,4) or HFHSD (P-HD, L-HD, n=9,10).

B) Ingenuity pathway analysis showing selection of top significantly enriched canonical pathways ranked by P-adjust.

C) Venn diagram for converse gene regulation by diet (P-RD x L-HD) and genotype (P-HD x L-HD). Red up-regulation, blue down-regulation.

D) Heat map for selected DEGs from groups in C.

E) RT-qPCR validation of DEGs (n=4,4,10,12) and comparison with RNA-seq counts (n=4,4,9,10) normalized to P-HD.

F) Hmgcr Immunostaining in P446L livers (RD and HD) and cytoplasmic H-scores. n=4,4 (RD); 9,9 (HD).

G. Correlation of GK activity and RNA-seq Gck gene counts (n=9,10)/

H) Venn diagram for common genes between the hepatocyte transcriptome (up-regulated by GK and down-regulated by GKRP, Figure 2G) and genes up-regulated by diet (P-RD x P-HD; L-RD x L-HD)

I) Correlation coefficient matrix for hepatocyte transcriptome (Figure 2: n=3 hepatocyte preparations,10 conditions) comparing expression of 17-cholesterol linked identified by the IPA analysis on P446L livers and 8 of 20 genes that were up-regulated by GK-overexpression and counter-regulated by GKRP in the hepatocyte study (Figure 2) showing significant (P < 0.05) positive correlations (green) and negative correlations (purple). The Z-score shows up-regulation orange, down regulation grey.

J) Correlation coefficient matrix for P446L mouse liver transcriptomes (P-RD, P-RD, P-HD, L-HD, n=27) for the same genes as in (H). The Z-score shows relative expression by experimental group (P-RD, L-RD, P-HD and L-HDL-HD).

Funding

MICA: Exploring a new perspective on the mechanism of action of Glucokinase Activators in liver, a preclinical study

Medical Research Council

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