Microarray Studies in High and Low RFI Cattle Reveal a Potential Role for Gonadotropin Releasing Hormone (GnRH) in Regulating Feed Efficiency

Abstract Text: Residual feed intake (RFI) is a heritable feed efficiency measure. Mechanisms underlying variation in feed efficiency are currently poorly understood. To address this issue, two divergent cohorts consisting of High (H) and Low (L) RFI individuals were created by assessing RFI in forty-eight Angus-sired steers during a 70 d feeding trial to identify steers with divergent RFI. Microarray studies using the Affymetrix Bovine Genome Array were then conducted on hypothalamic tissue (HT) RNA samples harvested from H and L RFI steers. The test diet was 50% sorghum-sudan silage, 50% grain (2.9 Mcal ME/kg DM). While on test, feed intake was recorded daily with BW and hip heights recorded at 14 day intervals. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and prior to harvest. Carcass and growth data were analyzed using a mixed model with RFI level (L, H) as the independent variable. The lsmeans for RFI were -1.25 and 1.51 for the L and H cohorts (P < .0001). Dry matter intake was higher for the H individuals versus the L steers (P < .0001) while on test BW gain was not different between the two groups (P < 0.73). Of the 24,000+ probes included on the Affymetrix Bovine Genome Array, 891 were found to be significantly different (P < 0.05) with 149 of these being highly different (P < 0.01) between high and low RFI.  Pathway analysis of the data set using Ingenuity Pathway Analysis software revealed that the pathways most heavily represented in the differentially expressed genes were consistent with the known functions of the central nervous system, specifically; increased cellular movement (important for synapse formation and neuronal communication), cell-to-cell communication and cellular development (P=1.34x10^-24, 9.54x10^-20,3.14x10^-17, respectively).  In terms of canonical pathways, dendritic cell maturation and interleukin signaling (P=3.56x10^-6 and 5.24x10^-6, respectively) were identified as differentially activated by RFI status of particular interest and warrant further investigation. Furthermore, GnRH signaling (including GnRH agonist and GnRH signaling) was predicted to be to be greater in H steers.  These findings are consistent with targeted gene expression assays using real-time PCR where GnRH mRNA abundance was lower in the arcuate nucleus of L steers. These data support the hypothesis that differences in hypothalamic neuropeptide gene expression underlie variation in feed efficiency in steers while the gonadotropin axis may also influence feed efficiency.

Keywords: RFI, steer, feed efficiency