Table 3.
Differential Activation of Upstream Regulators by Slc-HKO Livers Compared with WT Controls (Chow Diet, 3 months)
| Upstream regulator | Predicted activation state | Activation Z score | P value of overlap |
|---|---|---|---|
| PPARA | Inhibited | −2.9 | 2.97 × 10−07 |
| SLC27A2 | Activated | 3.1 | 6.59 × 10−06 |
| XBP1 | Activated | 3.8 | 1.68 × 10−05 |
| CLPP | Activated | 2.5 | 2.75 × 10−04 |
| ERN1 | Activated | 2.2 | 2.24 × 10−03 |
| PCK1 | Activated | 2.0 | 2.58 × 10−03 |
| KLF15 | Inhibited | −2.6 | 4.85 × 10−03 |
| LPL | Inhibited | −2.2 | 6.63 × 10−03 |
| ELL2 | Activated | 2.6 | 8.85 × 10−03 |
| SREBF1 | Activated | 2.0 | 9.04 × 10−03 |
| miR-223 | Activated | 2.7 | 1.46 × 10−02 |
| miR-30c-5p (and other miRNAs with seed GUAAACA) | Inhibited | −2.3 | 1.46 × 10−02 |
| MEX3A | Activated | 2.2 | 1.81 × 10−02 |
| PTPRR | Inhibited | −2.3 | 1.82 × 10−02 |
| ZBTB7B | Inhibited | −2.2 | 2.50 × 10−02 |
| MYCN | Activated | 2.2 | 2.59 × 10−02 |
| TP63 | Activated | 2.8 | 3.93 × 10−02 |
| miR-10 | Inhibited | −2.4 | 4.27 × 10−02 |
| TP73 | Activated | 2.2 | 4.88 × 10−02 |
“Upstream Regulator” is defined by Ingenuity Pathway Analysis as any molecule that can affect the expression of other molecules. Nineteen upstream regulators were identified (Z score less than −2 and >2; P value of overlap <0.05). Bold indicates metabolic relevance.
Slc-HKO, hepatocyte-specific Slc25a34 knockout; WT, wild type.