Table 3.
DREsa and Regions of AhR Enrichmentb in TCDD Responsive Genes Associated With Lipid and Carbohydrate Transport and Metabolism
| Gene ID | Gene symbol | Liver | Duodenum | Jejunum | ** of DREsa | ChIP peaks 2 hb | Functionc | Regulated byc |
| Xenobiotic metabolism | ||||||||
| 13076 | Cyp1a1 | 5799* | 222* | 22.7* | 7 | 4 | Xenobiotic metabolism | AhR |
| Fatty acid and triglyceride synthesis | ||||||||
| 14104 | Fasn | −2.8* | NC | NC | 4 | 1 | Fatty acid synthesis | SREBP, TR, LXR, cAMP, AMPK |
| 153674 | Acly | −2.6*** | nd | nd | 0 | 0 | Citrate metabolism | Oxaloacetate, ATP |
| 107476 | Acaca | −1.4*** | nd | nd | 3 | 5 | Malonyl CoA acylation | glucagon |
| 68393 | Mogat1 | 3.6* | NC | NC | 1 | 0 | Triglyceride synthesis | PPAR, CEBP |
| 233549 | Mogat2 | 3.0* | NC | 1.4* | 4 | 3 | ||
| 13350 | Dgat1 | 2.0 | 1.4 | 1.6* | 4 | 0 | ||
| 67800 | Dgat2 | 1.3 | 1.4 | 1.6 | 2 | 7 | ||
| Fatty acid transport | ||||||||
| 238055 | Apob | 2.5* | NC | 1.8* | 2 | 0 | VLDL and chylomicron assembly | APOBEC-1 |
| 16835 | Ldlr | 3.2* | 2.3* | NC | 2 | 4 | Lipoprotein uptake | LXR |
| 12491 | Cd36 | 4.4* | 2.7* | NC | 0 | 1 | Fatty acid uptake | PPAR, CEBPα, AMPK |
| 26457 | Slc27a1 | −2.9* | 2.3* | −5.8** | 2 | 0 | Mitochondrial β-oxidation | PPARα, PPARγ |
| 26568 | Slc27a3 | 2.7* | NC | NC | 1 | 0 | Unknown | |
| 26569 | Slc27a4 | 3.0* | 1.4** | 1.4** | 0 | 0 | Peroxisomal β-oxidation,CHOL-ester synthesis | PPARγ, SREBP1c |
| 14080 | Fabp1 | 2.9* | 1.4* | 1.7* | 2 | 4 | TAG synthesis, β-oxidation | PPARα, HNF4α |
| 11770 | Fabp4 | 1.4** | 1.5 | 2.5 | 0 | 0 | Chylomicron assembly | cJun, PPARγ |
| 117147 | Acsm1 | −2.0*** | nd | nd | 3 | 0 | Medium-chain fatty acid transport (mitochondrial β-oxidation) | Acetyl-CoA, malonyl-CoA, NADPH, NADH |
| 233799 | Acsm2 | −1.5*** | nd | nd | 0 | 0 | ||
| 20216 | Acsm3 | −1.6*** | nd | nd | 2 | 0 | ||
| 233801 | Acsm4 | −1.2*** | nd | nd | 0 | 0 | ||
| 14081 | Acsl1 | −1.4*** | nd | nd | 6 | 5 | Long-chain fatty acid transport (mitochondrial β-oxidation) | |
| 74205 | Acsl3 | −2.3*** | nd | nd | 0 | 0 | ||
| 50790 | Acsl4 | −1.3*** | nd | nd | 0 | 2 | ||
| Fatty acid metabolism | ||||||||
| 16956 | Lpl | 3.2*** | nd | nd | 2 | 0 | TAG metabolism of lipoproteins and chylomicrons | Insulin, glucagon, epinephrine |
| 109791 | Clps | 2.6*** | nd | nd | 0 | 0 | ||
| 18946 | Pnliprp1 | 3.7*** | nd | nd | 0 | 0 | ||
| 11343 | Mgll | 1.4*** | nd | nd | 9 | 0 | Monoglyceride metabolism | PPARα |
| 116939 | Pnpla3 | −3.3*** | nd | nd | 0 | 1 | TAG metabolism | |
| Glycolysis/Gluconeogenesis/Glycogen synthesis | ||||||||
| 18534 | Pck1 | −2.0*** | nd | nd | 0 | 1 | Gluconeogenesis | Insulin, glucagon, cAMP |
| 14377 | G6pc | −2.7*** | nd | nd | 1 | 5 | Insulin, glucose | |
| 18563 | Pcx | −1.3*** | nd | nd | 5 | 4 | ATP | |
| 103988 | Gck | −1.5*** | nd | nd | 3 | 2 | Glucose metabolism | G6P, insulin, glucagon |
| 212032 | Hk3 | 2.2*** | nd | nd | 1 | 0 | ||
| 232493 | Gys2 | −1.5*** | nd | nd | 2 | 4 | ||
Note. NC, no change; nd, not detected.
aDRE distributions were previously determined (Dere et al., 2011a). Only DREs satisfying a matrix similarity score of ≥ 0.85 were included.
bAhR enrichment was previously determined (Dere et al., 2011b).
cData from Boron and Boulpaep (2008), Hardwick et al. (2009), and Watkins (2008).
*p < 0.05 or **p < 0.01 for TCDD compared with vehicle, QRTPCR data at 24 h postdose. QRTPCR data were analyzed by Dunnett’s t-test, n = −5. *** for P1(t) ≥ 0.999 for microarray data at 168 h postdose (Dere et al., 2011a).