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Table 4 Summary of genes differentiating FUNG, FISH, and COMB. Summary of genes differentiating FUNG, FISH, and COMB. Included are a subset of the most important genes selected from Table 3. The predicted global metabolic effect (up or down regulation) mediated by the differentiating group relative to other groups, is shown in the first column. The 2nd column shows the differentiating group. The differentially regulated genes, and their direction of change, are shown in column 3, with signaling cascades in column 4. For example, relative to other groups, FUNG up regulated apoptosis via down regulation of the apoptosis inhibitor diap1, via JUN-RHOA signaling. TF, transcription factor.

From: How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

Metabolic effect of gene change Differentiating group Gene changes Signaling pathway
Amino acid: tyrosine & ornithine metabolism FUNG dct↓, sf3a2↑, oat↑ CTNB1
Protein synthesis FUNG eef1a1↓  
Apoptosis↑ FUNG Diaph1↓ (apoptosis inhibitor) JUN-RHOA
Apoptosis↓ FISH dvl2↓ CTNB1/MAPK9 and -10 activation
Apoptosis↑ FISH Camk2b↓ INS1/hRAS/SAG/I κBα, P27KIP1
Apoptosis↑ FISH Nfkbia↓ NFκB signaling
Apoptosis↑/↓ G1/S progression COMB atf4↓, atf5↓ bZIP TF
Biliary bicarbonate secretion↓ FISH<FUNG slc4a2↓  
Bile acid uptake by hepatocytes↓ FISH slc10a1↓  
Biliary cholesterol secretion↓ COMB aqp8↓ SREBP1a
Carbohydrate metabolism COMB foxa3↓, hnf3g↓, g6pc↓ foxa3: INS1-FOXA2
Carbohydrate metabolism COMB; FUNG<FISH bat2↓ CTNB1
Cell proliferation↑ FUNG<FISH dusp9↓ JUN-CDKN2A. DUSP phosphatases inhibit MK
Cell proliferation↑ FUNG ppp1ca↓ INS1-hRAS
Cell proliferation↑ FUNG>FISH Ptpra↑ activates Src tyr kinases
Cell proliferation↑ FUNG<FISH ptpn1↓, ppp2cb↓  
Cell proliferation↓ FUNG<FISH; COMB ighmbp2↓ TGFβ 1-HGF
Cell proliferation↓ FUNG cyp24↓ (↑1,25(OH)2D3) VDRE-PXR signaling
Cell proliferation↓ FUNG ccnb1↓ (codes cyclin B1) CDK1 activation
Cell proliferation↓ FUNG tcfeb↓, barx1↓, notch2↓  
Cell proliferation↓ FUNG<FISH; COMB tcfe3↓ bHLH-zip TF
Cell proliferation↑ FISH bop1↓ MYC
Cell proliferation↑/Lipid transport↑ FISH cd36↑ PPARα signaling
Cell proliferation↑/Lipid transport↑ FISH abce1↑ FABP-SNCA
Cell proliferation↓ FISH tcea2↓ MYC-POL2RA
Cell proliferation↓ FISH usf2↓ bHLH TF
Cell proliferation↓ FISH jund↓, yy1↓ bHLHzip TF: IL6-TNF signaling
Cell proliferation↓ FISH hoxa13↓ TGFβ 1-BMP2
Cell proliferation↓ FISH fgfr3↓ INS1-STAT3
Cell proliferation↓ FISH cdk4↓ D-cyclin-INK4a
Cell proliferation↓ FISH tef↓  
Cell proliferation FISH rab5c↓ (phosphatase; GTPase)  
Cell proliferation FISH eef2↓ (activity depends on P state)  
Cell proliferation↓ COMB plk1↓ (Zn finger) CTNB1
Cell proliferation↓ COMB Rgs16↑ JUN-TNF-G protein coupled receptor
Cell proliferation COMB atf5↓ bzip TF
Cell proliferation COMB ntrk1↓ (receptor tyr kinase) INS1/hRAS
Cell proliferation COMB eprs↓ (activity depends on P state) TGFβ 1-IKBKb
Clotting↓ FISH serpinc1↑  
Collagen synthesis↓ FUNG plod3↓  
Cytoskeletal effects COMB acta2↓, arhgef7↓, sn↓, tubb2↓, tubb3↓ CTNB1
FA β-Oxidation↑ ALL acadm↑, crat↑, cpt1a↑, cpt2↑, ech1↑ PPARα signaling
AcetylCoA biosynthesis↓ COMB acas2↓  
AcylCoa binding↓ COMB dbi↓ MYC
FA synthesis/desaturation↓ COMB acly↓ thrsp↓, fasn (FUNG<FISH)↓, scd↓ INS1, SREBP, PPARα, TNF
FA elongation↑ FISH elovl2/3↑  
Cyt P450 metabolism↑ FISH 4a10↑, 4a14↑ (affect ion channel activity, vascular tone) PPARα signaling
FA transported into liver↓ FUNG slc27a1↓ JUN-TNF-PPARα
Lipid transport↓ FISH fabp5↓ TGFβ 1-PPARα
Lipoprotein metabolism FUNG apoc1↓ INS1
Lipoprotein metabolism: reverse cholesterol transport↑ FISH apoe↑ (↓ cholesterol and TAG)  
Lipoprotein metabolism: transport↓ COMB apoa4↓ PPARα signaling
Galactose binding↓ FUNG lgal3↓ CTNB1
Heme synthesis FUNG alas1↑, alas2↓ INS1-STAT3
Hemoglobin synthesis↑ FISH>FUNG hba-a1↑, hbb-b1↑  
Immune system COMB tcf2↓, tcf7↑ MYC-PCAF-CREBP; CTNB1
Oxidative stress COMB hpx↓ TGFβ 1-LEP
Oxidative stress: aldehyde dehydrogenases↑ FISH aldh1a7↑, aldh2↑ aldh1a1↑ SREBP1a
Oxidative stress: peroxidases↑ FISH gpx1↑, prdx2↑, prdx4↑, mpo↑  
Oxidative stress: heat shock proteins FISH vs FUNG hspb1 (HSP25/27)↓, hspcb↑ ERK, PKCδ, TGFβ, p38, MK2/TNFα, IL1β, NFκB