Upstream regulator analysis identified 201 putative upstream regulators that could contribute to the observed changes in gene expression (Supplemental Table 3). Glucagon, glutamate, somatostatin and norepinephrine are identified as active, as were ILR1, IL17A, IL2 and LPS. Also noted as possible activators are CREBBP/CREM and protein kinases A and C. PPAR α and γ, HDAC4, mifepristone, cannabinol, morphine, taurine, testosterone, RXR, PXR, Insulin receptor, and steroid regulatory binding proteins Srebf1 and Srebf2 all appear to show reduced activity. Many circulating molecules and drugs are predicted to be active (e.g. have effects similar to those found after ethanol) or to be inactive (and potentially oppose those effects) (Table 5).
