Transcriptomic analysis by RNA sequencing reveals that hepatic interferon-induced genes may be associated with feed efficiency in beef heifers1

Abstract

In beef cattle, production feedstuffs are the largest variable input cost. Beef cattle also have a large carbon footprint, raising concern about their environmental impact. Unfortunately, only a small proportion of dietary energy is directed toward protein deposition and muscle growth whereas the majority supports body maintenance. Improving feed efficiency would, therefore, have important consequences on productivity, profitability, and sustainability of the beef industry. Various measures of feed efficiency have been proposed to improve feed utilization, and currently, residual feed intake (RFI) is gaining popularity. However, the cost associated with measuring RFI and the limited knowledge of the biology underlying improved feed efficiency make its adoption prohibitive. Identifying molecular mechanisms explaining divergence in RFI in beef cattle would lead to the development of early detection methods for the selection of more efficient breeding stock. The objective of this study was to identify hepatic markers of metabolic feed efficiency in replacement beef heifers. A group of 87 heifers were tested for RFI adjusted for off-test backfat thickness (RFIfat). Preprandial liver biopsies were collected from 10 high- and 10 low-RFIfat heifers (7 Hereford–Aberdeen Angus and 3 Charolais–Red Angus–Main Anjou per group) and gene expression analysis was performed using RNA sequencing and quantitative real-time PCR. The heifers used in this study differed in RFIfat averaging 0.438 vs. –0.584 kg DM/d in high- and low-RFIfat groups, respectively. As expected, DMI was correlated with RFIfat and ADG did not differ between high- and low-RFIfat heifers. Through a combination of whole transcriptome and candidate gene analyses, we identified differentially expressed genes involved in inflammatory processes including hemoglobin β (HBB), myxovirus resistance 1 interferon-inducible protein p78 (MX1), ISG15 ubiquitin-like modifier (ISG15), hect domain and RLD 6 (HERC6), and interferon-induced protein 44 (IFI44) whose mRNA abundance was lower (HBB) or higher (MX1, ISG15, HERC6, and IFI44) in low-RFIfat heifers. These genes have been shown to be directly or indirectly modulated by interferon signaling and involved with innate immunity. Our results suggest that more efficient heifers respond differently to hepatic proinflammatory stimulus, potentially expending less energy toward combating systemic inflammation and redirecting nutrients toward growth and protein accretion.

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

“…However, similar DEGs were not identified in the present study on dairy cattle, suggesting that the discrepancy may be based on the breed. However, some of our results are consistent with a study showing a connection between immune function and most of the DEGs associated with low and high RFI in beef cattle [31]. Alexandre et al (2015) [28] concluded that the DEGs related to feed efficiency and hepatic physiology were focused more towards the immune response, the metabolism of lipids and cholesterol and hepatic inflammation, which is also consistent with the findings of the present study.…”

“…Recently, an investigation of two divergent RFI groups in beef cattle using RNA-Sequencing [28, 31] revealed eight and seven significantly DEGs, respectively. However, similar DEGs were not identified in the present study on dairy cattle, suggesting that the discrepancy may be based on the breed.…”

A transcriptome multi-tissue analysis identifies biological pathways and genes associated with variations in feed efficiency of growing pigs

“…In cattle, contrasted results have rather been reported. Consistent with our results, the expression levels of some genes related to inflammatory processes were lower in liver of low RFI heifers [23] and an enrichment of transcriptomic networks for inflammatory response was conversely reported in the liver of low feed efficient, high RFI steers [13]. On the opposite, pathway analysis of DEG across muscle, adipose tissue and duodenum predicted immune system and inflammatory response to be increased in low RFI bulls [16].…”

Differential expression of genes related to gain and intake in the liver of beef cattle

“…Genes involved in cell proliferation were lower in transcript abundance during the restriction period, and cytokinesis, inflammation, and oxidative stress were higher in transcript abundance after the ad libitum feeding [22]. Paradis et al [23] used RNA sequencing to identify differentially expressed genes in liver biopsies from beef replacement heifers with low or high RFI adjusted to backfat thickness. They found seven DE genes, five of which are regulated by interferon signaling.…”

“…They also used qRT-PCR to identify DE genes and identified genes that play a role in oxidative stress and detoxification. These results showed that more efficient heifers may have an improved response to inflammation and may expend less energy combating pathogens than high RFI heifers [23]. Chen et al [8] saw a down-regulation of genes involved in inflammation and oxidative stress in high feed efficiency Angus bulls, and an up-regulation of those genes in the low efficiency bulls [8].…”