Journal of Immunology Research

Research Article

Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD

Table 2

(a) The 61 out of 71 mRNAs (85.9%) of glycolysis pathway enzyme genes are regulated in human and mouse NASH/NAFLD. Glycolysis pathway enzyme gene expression (PMID: 31153039) for human NASH studies (GSE17470 and GSE63067), MCD+HFD (GSE35961), HFC (GSE53381), MAT1A-KO (GSE63027), and GNMT-KO (GSE63027). The first human NASH study (GSE17470) upregulated 25 out of 71 (35.2%) and downregulated 5 out of 71 (7%) glycolysis enzymes. The second human NASH study (GSE63067) upregulated 5 out of 71 (7%) and downregulated 0 out of 71 (0%) glycolysis enzymes. The MCD+HFD model upregulated 20 out of 71 (28.2%) and downregulated 24 out of 71 (33.8%) glycolysis enzymes. The MAT1A-KO model upregulated 6 out of 71 (8.5%) and downregulated 13 out of 71 (18.3%) glycolysis enzymes. The GNMT-KO model upregulated 7 out of 71 (9.9%) and downregulated 4 out of 71 (5.6%) glycolysis enzymes. The HFCD model upregulated 17 out of 71 (23.9%) and downregulated 8 out of 71 (11.3%) glycolysis enzymes. The 71 glycolysis pathway genes are shown in Supplementary Table 3a. (b) The 13 out of 24 mRNA (54.2%) of acetyl-CoA generating enzyme are regulated in human and mouse NASH/NAFLD. Acetyl-CoA generating pathway enzyme gene expression (PMID: 31153039) for human NASH studies (GSE17470 and GSE63067), MCD+HFD (GSE35961), HFC (GSE53381), MAT1A-KO (GSE63027), and GNMT-KO (GSE63027). The first human NASH study upregulated 4 out of 24 (16.6%) and downregulated 0 out of 24 (0%) acetyl-CoA generation enzymes. The second human NASH study upregulated 1 out of 24 (4.2%) and downregulated 0 out of 24 (0%) acetyl-CoA generation enzymes. The MCD+HFD model upregulated 3 out of 24 (12.5%) and downregulated 7 out of 24 (29.2%) acetyl-CoA generation enzymes. The MAT1A-KO model upregulated 1 out of 24 (4.2%) and downregulated 4 out of 24 (16.7%) acetyl-CoA generation enzymes. The GNMT-KO model upregulated 2 out of 24 (8.3%) and downregulated 0 out of 24 (0%) acetyl-CoA generation enzymes. The HFCD model upregulated 7 out of 24 (29.2%) and downregulated 2 out of 24 (8.3%) acetyl-CoA generation enzymes. The 24 acetyl-CoA generating enzyme genes are shown in Supplementary Table 3b. (c) The 10 out of 10 mRNAs (100%) of mevalonate pathway enzyme genes are regulated in human and mouse NASH/NAFLD. Mevalonate pathway enzyme gene expression (PMID 31153039 and PMID 29328908) for human NASH studies (GSE17470 and GSE63067), MCD+HFD (GSE35961), HFC (GSE53381), MAT1A-KO (GSE63027), and GNMT-KO (GSE63027). The first human NASH study upregulated 2 out of 10 (20%) and downregulated 3 out of 10 (30%) mevalonate pathway enzymes. The second human NASH study upregulated 1 out of 10 (10%) and downregulated 0 out of 10 (0%) mevalonate pathway enzymes. The MCD+HFD model upregulated 7 out of 10 (70%) and downregulated 1 out of 10 (10%) mevalonate pathway enzymes. The MAT1A-KO model upregulated 4 out of 10 (40%) and downregulated 1 out of 10 (10%) mevalonate pathway enzymes. The GNMT-KO model upregulated 3 out of 10 (30%) and downregulated 0 out of 24 (0%) mevalonate pathway enzymes. The HFCD model upregulated 7 out of 10 (70%) and downregulated 0 out of 10 (0%) mevalonate pathway enzymes. The 10 mevalonate pathway enzyme genes are shown in Supplementary Table 3C.
(a)
PatientsMouse
GEO IDGSE17470GSE63067GSE35961GSE63027GSE63027GSE53381
ComparisonNASH vs. healthyNASH vs. healthyMCD+HFD vs. NCDMAT1A-KO vs. WTGNMT-KO vs. WTHFCD vs. NCD
Gene symbol
 ACSS14.47-2.67
 ACSS2-2.55-1.623.45
 ADH72.761.641.481.39
 AHD1A7.97
 ADH1B2.82
 ADH1C4.09
 ALDH1A36.34
 ALDH1B14.381.622.24-1.63
 ALDH26.33-1.70-1.501.59
 ALDH3A22.032.05-2.875.86
 ALDH3B12.49
 ALDH7A13.81-4.071.65
 ALDOA3.69
 ALDOC2.211.641.323.96
 DLAT-2.861.40-2.341.401.36
 ENO33.934.11
 FBP23.13
 HK12.73
 HK22.10
 HKDC1-1.855.361.60
 LDHA-1.79
 LDHB4.99
 PCK27.054.38-1.33
 PDHA11.91
 PDHB-1.39-1.72
 PFKFB13.641.631.62
 PFKFB42.691.62
 PFKP7.30-2.27
 PGAM11.44
 PGK1-6.501.75
 PGM11.682.701.71-1.64
 PKM5.27-2.76
 ADH441.77-2.88-1.51-2.01
 ADH54.73-1.331.45
 ADH65.42-4.71
 ADPGK-2.07-1.82
 ALDH3B2-1.67
 ALDH9A1-1.351.92
 ALDOB2.051.50-1.661.30
 BPGM-1.32-1.371.32
 DLD2.58-2.021.68
 ENO1-1.551.36
 ENO2-2.13
 FBP12.24-2.231.49
 G6PC-5.06-1.59
 GALM2.16-1.721.37
 GAPDH-1.61
 GCK17.03-33.70
 GPI1.95
 HK32.71-3.37
 LDHC-2.04
 PANK1-1.391.77
 PCK1-1.88-1.45
 PFKFB21.74
 PFKFB31.982-1.65-2.48
 PFKL1.738-1.37
 PFKM-1.98-1.49-1.31
 PGAM222.09-2.02
 PGM21.52
 PKLR1.738-1.80
 SLC2A29.160-1.761.36
% up25/71 (35.2%)5/71 (7%)20/71 (28.2%)6/71 (8.5%)7/71 (9.9%)17/71 (23.9%)
% down5/71 (7%)0/71 (0%)24/71 (33.8%)13/71 (18.3%)4/71 (5.6%)8/71 (11.3%)
(b)
HumanMouse
GEO IDGSE17470GSE63067GSE35961GSE63027GSE63027GSE53381
ComparisonNASH vs. healthyNASH vs. healthyMCD+HFD vs. NCDMAT1A-KO vs. WTGNMT-KO vs. WTHFCD vs. NCD
Gene symbol
 BDH12.331.89
 ACSS14.47-2.67
 ALDH26.33-1.70-1.501.59
 ACSS2-2.55-1.623.45
 ACAA22.83-1.511.381.49
 HADH1.501.37
 ADH1B2.82
 GOT11.79
 ACO1-1.411.45
 ACLY-2.40-1.361.75
 GLS3.27-2.40
 IDH12.83-1.40-1.451.60
 GLUD1-1.55
% up4/24 (16.6%)1/24 (4.16%)3/24 (12.5%)1/24 (4.2%)2/24 (8.3%)7/24 (29.2%)
% down0/24 (0%)0/24 (0%)7/24 (29.2%)4/24 (16.7%)0/24 (0%)2/24 (8.3%)
(c)
HumanMouse
GEO IDGSE17470GSE63067GSE35961GSE63027GSE63027GSE53381
ComparisonNASH vs. healthyNASH vs. healthyMCD+HFD vs. NCDMAT1A-KO vs. WTGNMT-KO vs. WTHFCD vs. NCD
Gene symbol
 IDI12.7781.5710.974
 IDI2-1.655
 HMGCS1-2.4401.8952.647.177
 MVD-1.7954.0031.3815.819
 MVK4.0965.4511.8583.895
 HMGCR2.0911.7642.663
 ACAT12.1351.3741.528
 PMVK1.453.366
 ACAT21.63
 HMGCS27.434-1.908-1.7381.681
% up2/10 (20%)1/10 (10%)7/10 (70%)4/10 (40%)3/10 (30%)7/10 (70%)
% down3/10 (30%)0/10 (10%)1/10 (10%)1/10 (10%)0/10 (0%)0/10 (0%)