Fig. 12

This gene network from the D1 vs. D9 contrast was functionally annotated by IPA as “Energy Production, Lipid Metabolism”. Panel a shows interactions among several lipogenic transcription factors [THRSPA, PPARG, PPARD and Kruppel like factor 15 (KLF15)] and their direct target genes, which are mainly expressed at greater levels in liver of D9 hatchlings. However, four target genes of KLF15, itself upregulated, were up-regulated in the liver of D1 hatchlings [i.e., hydroxyacyl-CoA dehydrogenase trifunctional multi-enzyme complex subunit alpha (HADHA), HADHB, enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) and pyruvate dehydrogenase kinase 4 (PDK4)]. Panel b shows known direct targets of PPARD and KLF15 and Ingenuity predictions of inhibition (blue arrows) or activation (dark orange arrows) of both the up-stream regulator and its respective gene targets. Ingenuity predicts inhibition of PPARD, due to the majority of downregulated target genes in the D1 vs. D contrast, which would lead to inhibition of 12 genes (blue arrows), whereas the blunt orange lines predict that PPARD actively inhibits cyclin dependent kinase 1 (CDK1), carnitine palmitoyltransferase 1A (CPT1A) and lipoprotein lipase (LPL), which are highly expressed in liver of fasted D1 hatchlings. Ingenuity predicts that activation of KLF15 in fasted D1 hatchlings would lead to activation of seven known target genes [solute carrier family 27 member 1 (SLC27A1), acyl-CoA synthetase long chain family member 1 (ACSL1), EHHADH, FABP5, HADHA, HADHB and PDK4], although uncertainty exists about KLF15’s action on five other AR-DEGs as indicated by the blunt yellow edges