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

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).

A) 热图展示PP和LL基因型P446L肝脏在常规饮食（P-RD，P-HD，n=4,4）或HFHSD（P-HD，L-HD，n=9,10）条件下的非监督聚类。
B) 通过P值校正后的P-adjust进行排序，展示Ingenuity通路分析中显著富集的通路。
C) 饮食（P-RD x L-HD）和基因型（P-HD x L-HD）对反向基因调控的文氏图。红色表示上调，蓝色表示下调。
D) 展示C组中选择的差异表达基因（DEGs）的热图。
E) 使用RT-qPCR验证DEGs（n=4,4,10,12）并与RNA测序计数（n=4,4,9,10）比较，以P-HD为基准进行归一化。
F) P446L肝脏（RD和HD）中的Hmgcr免疫染色和细胞质H评分。n=4,4（RD）；9,9（HD）。
G. GK活性与RNA测序Gck基因计数（n=9,10）/之间的相关性。
H) 文氏图展示肝细胞转录组（GK上调而GKRP下调，图2G）与饮食上调基因（P-RD x P-HD；L-RD x L-HD）之间的共有基因。
I) 肝细胞转录组的相关系数矩阵（图2：n=3个肝细胞制备，10个条件）比较由IPA分析在P446L肝脏中识别的与17-胆固醇相关的表达以及肝细胞研究中GK过表达上调并由GKRP反调节的8个20个基因的表达，显示显著（P < 0.05）的正相关（绿色）和负相关（紫色）。Z分数表示上调为橙色，下调为灰色。
J) P446L小鼠肝脏转录组的相关系数矩阵（P-RD，P-RD，P-HD，L-HD，n=27）展示与（H）中相同的基因，Z分数表示实验组（P-RD，L-RD，P-HD和L-HD）的相对表达。