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Hepatic mitochondrial function in Hereford steers with divergent residual feed intake phenotypes.

ABSTRACT: Variations in phenotypic expression of feed efficiency could be associated with differences or inefficiencies in mitochondria function due to its impact on energy expenditure. The aim of this study was to determine hepatic mitochondrial density and function in terms of respiration, gene and protein expression, and enzyme activity of mitochondrial respiratory complex proteins, in steers of divergent residual feed intake (RFI) phenotypes. Hereford steers (n = 111 and n = 122 for year 1 and 2, respectively) were evaluated in postweaning 70 d standard test for RFI. Forty-six steers exhibiting the greatest (n = 9 and 16 for year 1 and 2; high-RFI) and the lowest (n = 9 and 12 for year 1 and 2; low-RFI) RFI values were selected for this study. After the test, steers were managed together until slaughter under grazing conditions until they reached the slaughter body weight. At slaughter, hepatic samples (biopsies) were obtained. Tissue respiration was evaluated using high-resolution respirometry methods. Data were analyzed using a mixed model that included RFI group as fixed effect and slaughter date and year as a random effect using PROC MIXED of SAS. RFI and dry matter intake were different (P < 0.001) between low and high-RFI groups of year 1 and year 2. Basal respiration and maximum respiratory rate were greater (P ? 0.04) for low than high-RFI steers when complex II substrates (succinate) were supplied. However, when Complex I substrates (glutamate/malate) were used maximum respiratory capacity tended to be greater (P < 0.09) for low vs. high-RFI steers. Low-RFI steers presented greater mitochondria density markers (greater (P < 0.05) citrate synthase (CS) activity and tended (P ? 0.08) to have greater CS mRNA and mtDNA:nDNA ratio) than high-RFI steers. Hepatic expression SDHA, UQCRC1, and CYC1 mRNA was greater (P ? 0.02) and expression of NDUFA4, NDUFA13, SDHD, UQCRH, and ATP5E mRNA tended (P ? 0.10) to be greater in low than high-RFI steers. Hepatic SDHA protein expression tended (P < 0.08) to be greater while succinate dehydrogenase activity was greater (P = 0.04) and NADH dehydrogenase activity was greater (P = 0.03) for low than high-RFI steers. High-efficiency steers (low-RFI) probably had greater efficiency in hepatic nutrient metabolism, which was strongly associated with greater hepatic mitochondrial density and functioning, mainly of mitochondrial complex II.

SUBMITTER: Casal A

PROVIDER: S-EPMC6162574 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Hepatic mitochondrial function in Hereford steers with divergent residual feed intake phenotypes.

Casal Alberto A Garcia-Roche Mercedes M Navajas Elly Ana EA Cassina Adriana A Carriquiry Mariana M

Journal of animal science 20180901 10

Variations in phenotypic expression of feed efficiency could be associated with differences or inefficiencies in mitochondria function due to its impact on energy expenditure. The aim of this study was to determine hepatic mitochondrial density and function in terms of respiration, gene and protein expression, and enzyme activity of mitochondrial respiratory complex proteins, in steers of divergent residual feed intake (RFI) phenotypes. Hereford steers (n = 111 and n = 122 for year 1 and 2, resp ...[more]

PMID: 30032298

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Project description:Efficiency of feed utilization is important for animal production because it can reduce greenhouse gas emissions and improve industry profitability. However, the genetic basis of feed utilization in livestock remains poorly understood. Recent developments in molecular genetics, such as platforms for genome-wide genotyping and sequencing, provide an opportunity to identify genes and pathways that influence production traits. It is known that transcriptional networks influence feed efficiency-related traits such as growth and energy balance. This study sought to identify differentially expressed genes in animals genetically divergent for Residual Feed Intake (RFI), using RNA sequencing methodology (RNA-seq) to obtain information from genome-wide expression profiles in the liver tissues of Nelore cattle.Differential gene expression analysis between high Residual Feed Intake (HRFI, inefficient) and low Residual Feed Intake (LRFI, efficient) groups was performed to provide insights into the molecular mechanisms that underlie feed efficiency-related traits in beef cattle. A total of 112 annotated genes were identified as being differentially expressed between animals with divergent RFI phenotypes. These genes are involved in ion transport and metal ion binding; act as membrane or transmembrane proteins; and belong to gene clusters that are likely related to the transport and catalysis of molecules through the cell membrane and essential mechanisms of nutrient absorption. Genes with functions in cellular signaling, growth and proliferation, cell death and survival were also differentially expressed. Among the over-represented pathways were drug or xenobiotic metabolism, complement and coagulation cascades, NRF2-mediated oxidative stress, melatonin degradation and glutathione metabolism.Our data provide new insights and perspectives on the genetic basis of feed efficiency in cattle. Some previously identified mechanisms were supported and new pathways controlling feed efficiency in Nelore cattle were discovered. We potentially identified genes and pathways that play key roles in hepatic metabolic adaptations to oxidative stress such as those involved in antioxidant mechanisms. These results improve our understanding of the metabolic mechanisms underlying feed efficiency in beef cattle and will help develop strategies for selection towards the desired phenotype.

Project description:Abstract Although residual feed intake (RFI) is a moderately heritable trait that can be used as a selection tool, little is known about gene pathways and networks that affect it. Angus steers (n=1,460) from 72 contemporary groups (RFI: -6.44 to 7.52 kg/d) were genotyped with Illumina BovineHD or BovineSNP50 BeadChip assays. Significant SNP (P<0.05), identified by a genome-wide association analysis on RFI, were used as proxies for each of the annotated genes in the UMD3.1 bovine reference genome assembly. A gene set enrichment analysis-SNP was performed to identify gene sets and leading edge genes (LEG) and a network analysis was conducted to identify upstream and master regulators influencing RFI. Three enriched gene sets (normalized enrichment score>3.0) related to energy production and efficiency of energy usage (cellular respiration, GO:0045333, 20 LEG; Reactome respiratory electron transport, R-HSA-611105, 12 LEG; respiratory chain, GO:0070469, 12 LEG) were identified, corroborating evidence from RFI studies with cattle and other species. Additional enriched gene sets were synaptic vesicle (GO:0008021, 16 LEG), cell-cell junction (GO:0005911, 55 LEG), and protein localization to plasma membrane (GO:0072659, 20 LEG). Mediator complex subunit 30 (MED30) and RPTOR independent companion of MTOR complex 2 (RICTOR) were the most significant (P<10-10) upstream regulators. Part of the Mediator complex, MED30 plays a key role in transcription regulation and mediates lipid biosynthesis while RICTOR is a component of the mTOR complex, which regulates mitochondrial metabolism. Thyroid stimulating hormone receptor (TSHR), part of the hypothalamus-pituitary-thyroid axis that is essential for growth and metabolism and Ras homolog enriched in brain like 1 (RHEBL1), a gene that activates the mTOR complex in the brain, were the two most significant (P<10–14) master regulators. Gene set and pathway analyses suggest that biological processes related to energy metabolism and mitochondrial function play important roles in controlling RFI in cattle.

Project description:This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (-165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (-270 g/day). Low responses were observed on growth rate (-12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; -2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (-0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (-10% after five generations of selection) and activity (-21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.

Dataset Information

Hepatic mitochondrial function in Hereford steers with divergent residual feed intake phenotypes.

Publications

Hepatic mitochondrial function in Hereford steers with divergent residual feed intake phenotypes.

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