The significantly altered genes clustered into 22 biological pathways (Table 5; Supplemental Table 1). The oxidative phosphorylation and the mitochondrial dysfunction pathways nearly completely overlap: both contain 17 genes involved in oxidative phosphorylation. These include genes from complexes I, III, IV and V, including Atp5i, Atp5c1 and Atp5o (Tables 4, 5), and most of the genes showed 20–30%higher expression in the binge-drinking animals. EIF2 signaling was increased, with Atf3 (the gene with the second largest fold-change detected), Eif3g, and Eif2d all increased. The AMPK pathway is one of the central regulators of ATP levels and may play a role in the increased expression of genes involved in oxidative phosphorylation. Two large, related groups of pathways include signaling in the acute phase response and by many cytokines, including IL-6, IL-17A and TNFr1. Common genes in these pathways include transcription factors Fos and Jun, P21 protein activated kinases Pak6 and Pak3, insulin signaling IGF1 and Irs2, and Nfκbib. There are two Sertoli cell signaling pathways that have some of these same genes but also include tubulin genes Tuba1a and Tuba4a.
