Shifts in Hepatic Transcriptome Profiles of Growing Vs. Finished Beef Steers.

Transcriptome analysis was conducted to gain a greater understanding of hepatic metabolic shifts associated with the change in whole-body compositional gain of growing vs. finished beef steers. Weaned Angus steers (BW = 209 ± 29.4 kg) were randomly assigned (n = 8) to develop through lean (GROW, final BW = 301 kg) or lipid (FINISH, final BW = 576 kg) growth phases and individually fed enough of a cottonseed hull-based diet to achieve a constant ADG (1.5 kg/d). Marbling score (668, 296) and yield grade (3.65, 2.13) were greater (P < 0.01), but liver weight (1005, 1341 g/100 kg BW) less (P < 0.01), for FINISH vs. GROW steers, respectively. Total hepatic RNA was isolated, subjected to microarray (Bovine Affymetrix Gene 1.1 ST GeneChip) analysis, and differences in gene expression (false discovery rate < 10%; P < 0.01) between treatment groups determined by 1-way ANOVA (Partek Genomics Suite). Expression of 405 mRNA was increased (5 to 567%) and 695 (6 to 638%) decreased in FINISH vs. GROW steers. Bioinformatic (Ingenuity Pathway Analysis) analysis found that the top functional gene category was cell death and survival (47 genes; P ≤ 0.025) and the top canonical cell signaling pathway was calcium-induced T lymphocyte apoptosis (13 genes; P ≤ 0.0005). Functional analysis of canonical metabolic pathways found that FINISH steers had increased (P ≤ 0.009; 17 to 414%) capacities for ammonia (GLS2, GLUD1, GPT2), Arg (OAT, GOT1, ASS1, ASL), and urea production (ARG2), and shunting of amino acid carbons into pyruvate (ALT2, SDS, LDHB). For carbohydrate metabolism, capacity for glycolysis (PGK1, PKM2) was inhibited (P ≤ 0.003; 19 and 42%), whereas glycogen synthesis (GYG2, GYS2) was greater (P ≤ 0.002; 30 and 31%), in FINISH steers. For lipid metabolism, FINISH steers showed decreased (P ≤ 0.008; 28 to 163%) capacity for fatty acid activation (ACSL5, ACSF2) and desaturation (SCD, FADS1, FADS2), but increased (P ≤ 0.009; 26 to 61%) capacity for fatty acid β-oxidation (ACADL, ACAA1) and lipid storage (LIPA, PLIN3). In addition, redox capacity (GPX1, GSS, GGT1) and inflammatory responses (NOS2, SOCS2, CCL2, IL6R, TLR3) were decreased (P ≤ 0.008; 18 to 191%) in FINISH steers. Network analysis identified liver X receptor/retinoid X receptor activation as the most probable (P = 0.015) mechanism coordinating lipid metabolism and immune response events. These findings elaborate the shift in hepatic metabolic capacities as compositional gain shifted from lean to lipid phenotype in beef steers.