Diet Modifies Pioglitazone’s Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression

Table 1

Gene set analysis on RNA-Seq data from WT Pio-treated vs. Pio-untreated mice on control or HFD (as designated).

Gene set name (# in Hallmark set)	Description	Overlap	value
(a) Induced by Pio in WT mice on control diet
FATTY_ACID_METABOLISM [158]	Genes encoding proteins involved in metabolism of fatty acids.	51	4.84^-33
ADIPOGENESIS [200]	Genes upregulated during adipocyte differentiation (adipogenesis).	48	6.52^-25
BILE_ACID_METABOLISM [112]	Genes involve in metabolism of bile acids and salts.	30	3.36^-17
CHOLESTEROL_HOMEOSTASIS [74]	Genes involved in cholesterol homeostasis.	22	7.81^-14
OXIDATIVE_PHOSPHORYLATION [200]	Genes encoding proteins involved in oxidative phosphorylation.	32	9.78^-12
PEROXISOME [104]	Genes encoding components of peroxisome.	21	7.38^-10
UV_RESPONSE_DN [144]	Genes down-regulated in response to ultraviolet (UV) radiation.	24	1.98^-9
MYC_TARGETS_V1 [200]	A subgroup of genes regulated by MYC—version 1 (v1).	28	3.84^-9
INTERFERON_GAMMA_RESPONSE [200]	Genes upregulated in response to IFNG (GeneID=3458).	26	6.74^-8
(b) Induced by Pio in WT mice on HFD
FATTY_ACID_METABOLISM [158]	Genes encoding proteins involved in metabolism of fatty acids.	32	1.32^-28
OXIDATIVE_PHOSPHORYLATION [200]	Genes encoding proteins involved in oxidative phosphorylation.	33	9.38^-27
ADIPOGENESIS [200]	Genes upregulated during adipocyte differentiation (adipogenesis).	32	1.13^-25
PEROXISOME [104]	Genes encoding components of peroxisome.	20	7.76^-18
BILE_ACID_METABOLISM [112]	Genes involve in metabolism of bile acids and salts.	14	5.33^-10
GLYCOLYSIS [200]	Genes encoding proteins involved in glycolysis & gluconeogenesis.	14	8.69^-7
(c) Suppressed by Pio in WT mice on control diet
UV_RESPONSE_UP [158]	Genes upregulated in response to UV radiation.	35	9.3^-16
HEME_METABOLISM [200]	Genes involved in metabolism of heme & erythroblast differentiation.	32	1.43^-10
MTORC1_SIGNALING [200]	Genes upregulated through activation of mTORC1 complex.	28	3.4^-8
P53_PATHWAY [200]	Genes involved in p53 pathways and networks.	28	3.4^-8
APOPTOSIS [161]	Genes mediating apoptosis by activation of caspases.	24	8.69^-8
HYPOXIA [200]	Genes upregulated in response to low oxygen levels.	27	8.69^-8
DNA_REPAIR [150]	Genes involved in DNA repair.	23	8.69^-8
XENOBIOTIC_METABOLISM [200]	Genes encoding proteins that process drugs & other xenobiotics.	26	2.71^-7
UNFOLDED_PROTEIN_RESPONSE [113]	Genes upregulated during unfolded protein response.	19	2.71^-7
MYC_TARGETS_V1 [200]	A subgroup of genes regulated by MYC - version 1 (v1).	25	9.04^-7
(d) Suppressed by Pio in WT mice on HFD
No overlaps found

Using the Broad Institute platform with the Hallmark gene sets platform to identify the top 10 categories with (see text for details).