BP Figure 5: Liver transcriptome analysis in P446L mice after 20 wk on HFHSD -/+ AZD1656: lesser impact of AZD1656 treatment compared with P446L genotype.

A) Venn diagram for differentially expressed genes (DEGs adjusted P < 0.05) by AZD1656 treatment: PP- vs PP+ (26 DEGs) and LL- vs LL+ (13 DEGs); or by genotype PP- vs LL- (150 DEGs), PP+ vs LL+ (25 DEGs). Blue, common genes similar direction; red, common genes opposite direction. B) Ingenuity Pathway Analysis: showing top enriched pathways by genotype (PP-vs LL-) or by AZD1656 treatment (PP-/PP+ or LL-/LL+) showing Z-scores for pathway flux and –log (P-value). C-E) Genes that are differentially expressed by PP- vs LL- genotype show smaller but directionally similar changes by AZD1656 treatment in PP mice. Z-scores for gene counts and median and range of genes shown. **P<0.001, *P<0.02 effect of AZD1656; ##P<0.0001 genotype effect, one-way ANOVA. C) Z-scores for DEGs by PP>LL genotype (150 DEGs adjusted P < 0.05) showing relative gene counts for the 4 groups of mice (PP-, PP+, LL-, LL+) of the upregulated DEGs (n=49, upper panel) and downregulated DEGs (n=101). D) Z-scores of gene counts of GK and GKRP-responsive genes that are significantly elevated by LL genotype. E) Z-scores of gene counts of cholesterol homeostasis linked genes that are significantly up-regulated or down-regulated by LL genotype. F) Correlation of phenotypic traits (liver weight, liver cholesterol, liver triglyceride, blood glucose and insulin and blood triglycerides and blood cholesterol Total, LDL< HDL) with corresponding gene counts of GK-GKRP responsive genes identified in [35] and cholesterol homeostasis linked genes.