Gene expression profiling indicates an increased capacity for proline, serine, and ATP synthesis and mitochondrial mass by the liver of steers grazing high vs. Low endophyte-infected tall fescue

Grazing Neotyphodium coenophialum– infected forages results in a variety of reduced animal performance parameters, collectively known as “fescue toxicosis.” The initial, limited evaluations of hepatic mechanisms affected by fescue toxicosis have used transcriptomic expression profiling of experimental phenotypes developed by short-term feeding of concentrated ergot alkaloids or fescue seeds to rodents and steers. To assess the effects of fescue toxicosis in growing cattle using a commercially relevant phenotype, we induced fescue toxicosis in beef steers by summer-long grazing (89 to 105 d) of a single high toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) vs. a low toxic endophyte tall fescue– mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). High toxic endophyte tall fescue–mixed pasture steers had decreased BW (313 vs. 338 kg) and an increased potential for hepatic gluconeogenesis from AA-derived carbons. To gain a greater perspective into fescue toxicosis–induced hepatic metabolism and identify candidate regulatory mechanisms, the goal of the current research was to examine liver samples for changes in gene (mRNA) expression profiles using a Bovine Affymetrix microarray and selected reverse-transcription PCR and immunoblot analyses. The expression (false discovery rate < 10%; P < 0.01) of 147 genes was increased (7 to 268%) and that of 227 was decreased (4 to 87%) in livers of HE vs. LE steers. The top (1) functional gene category was cell-mediated immune response (33 genes; P ≤ 0.012), (2) canonical cell signaling pathway was primary immunodeficiency signaling (8 genes; P ≤ 0.0003), and (3) canonical metabolic pathways were oxidative phosphorylation (5 genes; P ≤ 0.016) and purine metabolism (8 genes; P ≤ 0.029). High toxic endophyte tall fescue–mixed pasture steers had increased (P ≤ 0.022) expression of genes critical for increased (1) Pro (PYCR1) and Ser (PSPH) synthesis, (2) shunting of AA carbons into pyruvate (ALT2) and ATP synthesis (NDUFC1, NDUFV2, UCRC, COX4, ATP5D, and ATP5F1), and (3) mitochondrial mass (COX4). Targeted reverse-transcribed PCR or immunoblot assays corroborated (P ≤ 0.035) these latter microarray findings for PYCR1, PSPH, ALT2, PEPCK, and COX4. Moreover, network analysis identified glucocorticoid receptor–mediated signaling as the most probable mechanism to coordinate the above findings. These results greatly extend our knowledge of the consequences of summer-long grazing of endophyte-infected tall fescue to the hepatic metabolism of growing steers.