Chemotherapy diminishes lipid storage capacity of adipose tissue in a preclinical model of colon cancer

Table 2 Activated and inhibited upstream regulators predicted by IPA following 2 cycles of chemotherapy

Upstream regulator	Molecular type	Predicted activation state	Activation Z-score*	P-value of overlap	Target molecules in differentially expressed dataset
PPARGC1A	Transcription regulator	Inhibited	−4.379	2.17E-19	ACACA, ACADVL, ACAT1, ATP5O, CAT, COX5A, CS,DLAT, FASN, IDH3A, MDH2, ME1, MT-CO2, NDUFV2, PCK1, PDHA1, PGAM1, PRDX3, SLC2A4,UQCRFS1
PPARγ	Ligand-dependent nuclear receptor	Inhibited	−4.06	1.629E-23	ACAA1, ACACA, ACLY, ATP5O, CAT, CPT2, CS, DLAT, FABP1, FASN, FDPS, GAPDH, GPD1,GPT, IDH1, IVD, KRT18, LIPE, ME1, MGLL, PC, PCK1, PDHB, PYGL, RPSA, SCP2, Slc25a1, SLC2, TKT
PPARα	Ligand-dependent nuclear receptor	Inhibited	−2.97	4.41E-16	ACAA1, ACACA, ACADVL, ACAT1, ACAT2, CAT, CPT2, CS, DBI, FABP1, FASN, FDPS, GPD1, GPT, MGLL,MT-CO2, PC, PCK1, PRDX6, SCP2, SLC2A4, UQCRC1
MYC	Transcription regulator	Inhibited	−2.61	2.27E-12	ACACA, ACAT1, AK2, ALDOA, CANX, CAPNS1, CPT2, DBI, ENO1, FABP1, FASN, GAPDH, GCSH, GPT, HSPE1, IDH1, IDH2, LUM, NDRG2, PCK1, PDHA1, PGAM1, PHB, PHB2, PRDX3, SLC25A5, TKT
SREBF1	Transcription regulator	Inhibited	−2.13	7.82E-09	ACACA, ACLY, ALDOC, DBI, FASN, FDPS, GPX3, IDH1, PCK1, THRSP, UQCRFS1
MAP4K4	Kinase	Activated	3.44	8.13 E-13	ACACA, ACADVL, ACLY, DLAT, FASN, IVD, MGLL, PGAM1, SCP2, SLC2A4, UQCRC1, UQCRFS1
5-Fluorouracil	Chemical drug	Activated	3.21	1.30E-11	ALDOA, ATP5O, CANX, CAPNS1, ECHS1, FDPS, GAPDH, HSPE1, IDH2, NDUFV2, PSMA7, RPS8, SLC25A5, UQCRC2

*Z > 2 and Z < −2 predict activation and inhibition of the upstream regulator, respectively. The p-value indicates the significance of the overlap between the molecules targeted by the upstream regulator in the IPA database and the experimental dataset. Abbreviations: PPARγ, Peroxisome proliferator-activated receptor gamma; PPARα, Peroxisome proliferator-activated receptor alpha; PPARGC1A, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; SREBF1 (SREBP1c), Sterol regulatory element binding transcription factor 1; MAP4K4, Mitogen-activated protein kinase kinase kinase kinas

ISSN: 1476-511X