Background
Methods
Animals and diets
Atherosclerosis quantification
Microarray analysis
Pathways analysis
Statistical analyses
Results
Diabetogenic diet induces obesity and atherosclerosis in Ldlr−/−mice
GSEA revealed common dysregulated pathways in AT and AO from obese mice
DPa
| NESd
| NOM p-Vale
| FDRf
| IRPg
| MRPh
| Name | ||||
---|---|---|---|---|---|---|---|---|---|---|
ATb
| AOc
| AT | AO | AT | AO | AT | AO | |||
x
|
x
|
2.43
|
1.35
|
<0.001
|
0.047
|
0.000
|
0.098
|
E2F targets
| ||
x
|
x
|
2.39
|
1.74
|
<0.001
|
<0.001
|
0.000
|
0.004
|
G2 M checkpoint
| ||
x
|
x
|
2.15
|
2.27
|
<0.001
|
<0.001
|
0.000
|
0.000
|
x
|
Allograft rejection
| |
x
|
x
|
2.12
|
2.33
|
<0.001
|
<0.001
|
0.000
|
0.000
|
x
|
Inflammatory response
| |
x
|
x
|
2.08
|
1.99
|
<0.001
|
<0.001
|
0.000
|
0.001
|
x
|
IL6 JAK STAT3 signaling
| |
x
|
x
|
1.99
|
1.90
|
<0.001
|
<0.001
|
0.000
|
0.001
|
Epithelial mesenchymal transition
| ||
x
|
x
|
1.97
|
1.97
|
<0.001
|
<0.001
|
0.000
|
x
|
TNFA signaling via NFKB
| ||
x
|
x
|
1.88
|
1.75
|
<0.001
|
<0.001
|
0.000
|
Mitotic spindle
| |||
x
|
x
|
1.86
|
2.10
|
<0.001
|
<0.001
|
0.000
|
0.000
|
Complement
| ||
x
|
x
|
1.86
|
2.10
|
<0.001
|
<0.001
|
0.000
|
x
|
Kras signaling up
| ||
x
|
x
|
1.81
|
1.41
|
0.002
|
0.045
|
0.001
|
Protein secretion
| |||
x
|
x
|
1.72
|
1.89
|
<0.001
|
<0.001
|
0.004
|
0.001
|
Apoptosis
| ||
x | x |
1.63
|
–1.34
|
0.001
|
0.026
|
0.008
|
0.091
| x |
MTORC1 signaling
| |
x
|
x
|
1.60
|
2.35
|
0.001
|
<0.001
|
0.011
|
0.000
|
x
|
Interferon gamma response
| |
x
|
x
|
1.58
|
1.61
|
0.021
|
0.021
|
0.013
|
0.011
|
x
|
Angiogenesis
| |
x
|
x
|
1.50
|
1.48
|
0.006
|
0.012
|
0.027
|
0.035
|
Coagulation
| ||
x | 1.48 | 0.012 | 0.030 | Unfolded protein response | ||||||
x | 1.43 | 0.015 | 0.047 | MYC targets V1 | ||||||
x | 1.41 | 0.024 | 0.051 | x | Androgen response | |||||
x | 1.36 | 0.027 | 0.073 | x | IL2 STAT5 signaling | |||||
x
|
x
|
1.34
|
1.68
|
0.024
|
<0.001
|
0.084
|
P53 pathway
| |||
x
|
x
|
−1.45
|
−1.72
|
0.016
|
<0.001
|
0.036
|
0.004
|
x
|
Peroxisome
| |
x |
−1.56
|
<0.001
|
0.000
|
Myogenesis
| ||||||
x
|
x
|
−1.65
|
−2.14
|
<0.001
|
<0.001
|
0.000
|
0.000
|
x
|
Bile acid metabolism
| |
x
|
x
|
−1.86
|
–1.46
|
<0.001
|
0.003
|
0.000
|
0.038
|
Xenobiotic metabolism
| ||
x
|
x
|
–2.17
|
–2.40
|
<0.001
|
<0.001
|
0.000
|
0.000
|
x
|
Fatty acid metabolism
| |
x
|
x
|
–2.44
|
−2.15
|
<0.001
|
<0.001
|
0.000
|
0.000
|
x
|
Oxidative phosphorylation
| |
x
|
x
|
−3.06
|
−2.38
|
<0.001
|
<0.001
|
0.000
|
0.000
|
x
|
Adipogenesis
| |
x | 2.08 | <0.001 | 0.000 | x | Interferon alpha response | |||||
x | 1.72 | <0.001 | 0.005 | Heme metabolism | ||||||
x | 1.63 | 0.001 | 0.010 | Apical junction | ||||||
x | 1.50 | 0.007 | 0.031 | x | Hypoxia | |||||
x | –1.77 | <0.001 | 0.002 | Spermatogenesis |
Single gene analysis of inflammatory response and oxidative phosphorylation pathways
Rank metric score | Gene symbol | Gene name | |
---|---|---|---|
ATa
| AOb
| ||
4.554 | 2.000 |
Il7r
|
Interleukin 7 receptor
|
3.713 | 2.000 |
C3ar1
|
Complement component 3a receptor 1
|
3.652 | 0.928 |
Emr1
|
Adhesion G protein-coupled receptor E1
|
3.489 | 0.579 |
Tlr1
|
Toll-like receptor 1
|
3.298 | 1.000 |
Rgs1
|
Regulator of G-protein signalling 1
|
3.285 | 0.576 |
Semad4d
|
Semaphorin 4D
|
3.205 | 0.940 |
Cybb
|
Cytochrome b-245 heavy chain
|
3.175 | 0.445 |
Kcnj2
|
Inward rectifier potassium channel 2
|
3.111 | 0.779 |
C5ar1
|
C5a anaphylatoxin chemotactic receptor 1
|
3.037 | 1.000 |
Cd48
|
CD48 antigen
|
2.961 | 1.000 |
Pik3r5
|
Phosphoinositide-3-kinase, regulatory subunit 5, p101
|
2.626 | 0.992 |
Ptafr
|
Platelet-activating factor receptor
|
2.422 | 0.894 |
Ptpre
|
Protein tyrosine phosphatase, receptor type, E
|
2.364 | 0.716 |
P2rx4
|
Purinergic receptor P2X, ligand-gated ion channel, 4
|
2.346 | 2.000 |
Timp1
|
Tissue inhibitor of metalloproteinase 1
|
2.197 | 2.000 |
Il10ra
|
Interleukin 10 receptor, alpha
|
1.692 | 0.519 |
Plaur
|
Plasminogen activator, urokinase receptor
|
1.594 | 0.496 |
Clec5a
|
C-type lectin domain family 5, member a
|
1.535 | 0.361 |
Gna15
|
Guanine nucleotide binding protein, alpha 15
|
1.452 | 0.922 |
Ccl2
|
Chemokine (C–C motif) ligand 2
|
1.303 | 0.273 |
Ifnar1
|
Interferon (alpha and beta) receptor 1
|
1.129 | 0.957 |
Ccl7
|
Chemokine (C–C motif) ligand 7
|
1.090 | 1.000 |
Csf3r
|
Colony stimulating factor 3 receptor (granulocyte)
|
0.921 | 0.460 |
Il1r1
|
Interleukin 1 receptor, type I
|
0.905 | 0.697 |
Ccl5
|
Chemokine (C–C motif) ligand 5
|
0.882 | 0.782 |
Icam1
|
Intercellular adhesion molecule 1 (CD54), human rhinovirus receptor
|
0.806 | 0.277 |
Slc11a2
|
Solute carrier family 11, member 2
|
Rank metric score | Gene symbol | Gene name | |
---|---|---|---|
ATa
| AOb
| ||
−2.2950 | −0.4060 |
Maob
|
Monoamine oxidase B
|
−2.0570 | −0.3260 |
Bckdha
|
Branched chain keto acid dehydrogenase E1, alpha polypeptide
|
−2.0250 | −0.8910 |
Aldh6a1
|
Aldehyde dehydrogenase 6 family, member A1
|
−2.0020 | −0.2060 |
Echs1
|
Enoyl CoA hydratase, short chain, 1, mitochondrial
|
−1.7080 | −0.3710 |
Cox8a
|
Cytochrome c oxidase subunit 8a
|
−1.4980 | −0.7180 |
Phyh
|
Phytanoyl–CoA hydroxylase
|
−1.4240 | −0.1680 |
Cox4i1
|
Cytochrome c oxidase subunit IV isoform 1
|
−1.3880 | −0.3800 |
Aco2
|
Aconitase 2, mitochondrial
|
−1.3400 | −0.2640 |
Acat1
|
Acetyl-Coenzyme A acetyltransferase 1
|
−1.3350 | −0.2220 |
Ndufb8
|
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8
|
−1.3200 | −0.1620 |
Ndufv1
|
NADH dehydrogenase (ubiquinone) flavoprotein 1
|
−1.3060 | −0.3470 |
Atp5d
|
ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit
|
−1.2750 | −0.2330 |
Ndufs7
|
NADH dehydrogenase (ubiquinone) Fe–S protein 7
|
−1.2670 | −0.4190 |
Ndufa4
|
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4
|
−1.2370 | −0.2430 |
Gpx4
|
Glutathione peroxidase 4
|
−1.2260 | −0.4390 |
Pdha1
|
Pyruvate dehydrogenase E1 alpha 1
|
−1.2060 | −0.4440 |
Sdhc
|
Succinate dehydrogenase complex, subunit C, integral membrane protein
|
−1.2030 | −0.3650 |
Cs
|
Citrate synthase
|
−1.1660 | −0.3270 |
Ndufa1
|
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1
|
−1.1510 | −0.2410 |
Ndufa8
|
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 8
|
−1.1450 | −0.1990 |
Cox6b1
|
Cytochrome c oxidase subunit Vib polypeptide 1
|
−1.1290 | −0.3140 |
Mrps15
|
Mitochondrial ribosomal protein S15
|
−1.1150 | −0.2280 |
Idh3 g
|
Isocitrate dehydrogenase 3 (NAD+) gamma
|
−1.0870 | −0.1990 |
Acadvl
|
Acyl-Coenzyme A dehydrogenase, very long chain
|
−1.0820 | −0.1850 |
Ndufa9
|
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9
|
−1.0620 | −0.3370 |
Cox6a1
|
Cytochrome c oxidase subunit VIa polypeptide 1
|
−1.0570 | −0.2870 |
Ndufc1
|
NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1
|
−1.0470 | −0.1760 |
Mfn2
|
Mitofusin 2
|
−1.0230 | −0.5940 |
Pdhb
|
Pyruvate dehydrogenase (lipoamide) beta
|
−1.0140 | −0.3930 |
Idh3b
|
Isocitrate dehydrogenase 3 (NAD+) beta
|
−0.9750 | −0.5050 |
Atp5g3
|
ATP synthase, H + transporting, mitochondrial F0 complex, subunit C3 (subunit 9)
|
−0.9440 | −0.1990 |
Uqcrfs1
|
Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1
|
−0.9060 | −0.2240 |
Mrpl34
|
Mitochondrial ribosomal protein L34
|
−0.8870 | −0.2150 |
Uqcrh
|
Ubiquinol-cytochrome c reductase hinge protein
|
−0.8840 | −0.3650 |
Grpel1
|
GrpE−like 1, mitochondrial
|
−0.8440 | −0.2340 |
Uqcrc2
|
Ubiquinol-cytochrome c reductase core protein 2
|
−0.8300 | −0.1600 |
Ndufb6
|
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6
|
−0.8010 | −0.5270 |
Ldhb
|
Lactate dehydrogenase B
|
−0.7460 | −0.2100 |
Phb2
|
Prohibitin 2
|
−0.7320 | −0.2170 |
Mrpl11
|
Mitochondrial ribosomal protein L11
|
−0.7270 | −0.4530 |
Cox6c
|
Cytochrome c oxidase subunit VIc
|
−0.7160 | −0.6190 |
Cox5b
|
Cytochrome c oxidase subunit Vb
|
−0.7090 | −0.1590 |
Suclg1
|
Succinate-CoA ligase, GDP-forming, alpha subunit
|
−0.7080 | −0.2300 |
Cox7b
|
Cytochrome c oxidase subunit VIIb
|
−0.7030 | −0.1930 |
Atp5j
|
ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F
|
−0.6970 | −0.3770 | Cox5a | Cytochrome c oxidase subunit Va |
−0.6920 | −0.2190 |
Dlst
|
Dihydrolipoamide S-succinyltransferase
|
−0.6890 | −0.2280 |
Atp5 h
|
ATP synthase, H+ transporting, mitochondrial F0 complex, subunit D
|
−0.6880 | −0.3350 |
Mdh1
|
Malate dehydrogenase 1, NAD (soluble)
|
−0.6860 | −0.3760 |
Ndufb3
|
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3
|
−0.6670 | −0.2560 |
Mrpl35
|
Mitochondrial ribosomal protein L35
|
−0.6340 | −0.2650 |
Prdx3
|
Peroxiredoxin 3
|
−0.6270 | −0.2690 |
Ndufa5
|
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5
|
−0.6050 | −0.2480 |
Ndufb5
|
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5
|
−0.5830 | −0.5650 |
Sdhd
|
Succinate dehydrogenase complex, subunit D, integral membrane protein
|
−0.5760 | −0.1720 |
Ndufs8
|
NADH dehydrogenase (ubiquinone) Fe–S protein 8
|