Progesterone signalling in broiler skeletal muscle is associated with divergent feed efficiency

Background: We contrast the pectoralis muscle transcriptomes of broilers selected from within a single genetic line expressing divergent feed efficiency (FE) in an effort to improve our understanding of the mechanistic basis of FE. Results: Application of a virtual muscle model to gene expression data pointed to a coordinated reduction in slow twitch muscle isoforms of the contractile apparatus (MYH15, TPM3, MYOZ2, TNNI1, MYL2, MYOM3, CSRP3, TNNT2), consistent with diminishment in associated slow machinery (myoglobin and phospholamban) in the high FE animals. These data are in line with the repeated transition from red slow to white fast muscle fibres observed in agricultural species selected on mass and FE. Surprisingly, we found that the expression of 699 genes encoding the broiler mitoproteome is modestly–but significantly–biased towards the high FE group, suggesting a slightly elevated mitochondrial content. This is contrary to expectation based on the slow muscle isoform data and theoretical physiological capacity arguments. Reassuringly, the extreme 40 most DE genes can successfully cluster the 12 individuals into the appropriate FE treatment group. Functional groups contained in this DE gene list include metabolic proteins (including opposing patterns of CA3 and CA4), mitochondrial proteins (CKMT1A), oxidative status (SEPP1, HIG2A) and cholesterol homeostasis (APOA1, INSIG1). We applied a differential network method (Regulatory Impact Factors) whose aim is to use patterns of differential co-expression to detect regulatory molecules transcriptionally rewired between the groups. This analysis clearly points to alterations in progesterone signalling (via the receptor PGR) as the major driver. We show the progesterone receptor localises to the mitochondria in a quail muscle cell line. Conclusions: Progesterone is sometimes used in the cattle industry in exogenous hormone mixes that lead to a ~20% increase in FE. Because the progesterone receptor can localise to avian mitochondria, our data continue to point to muscle mitochondrial metabolism as an important component of the phenotypic expression of variation in broiler FE

The role of Protein Degradation in Cancer Cachexia in Female Tumor Bearing Mice

Background: Cancer is a leading cause of death in the world in which half of the people affected by this disease die from its effects. Cancer-cachexia is a syndrome associated with the significant loss of skeletal muscle mass and function, which cannot be fully reversed by nutritional intervention alone and in turn, impairs the host. Cancer-cachexia affects 50-80% of cancer patients and is a primary cause of death accounting for 20-40% of cancer related deaths. Efforts to reverse the effects of cancer-related cachexia have been largely unsuccessful and have primarily focused on the late stages of CC. Methods: Lewis Lung Carcinoma (LLC) was injected into C57BL6/J mice into their hind flank at 8 weeks of age. The tumor was allowed to develop for a LT and HT group and was compared to a PBS control. Results: Tumor weight was significantly higher in HT mice in comparison to LT mice. Gastrocnemius and plantaris weight in LT and HT in comparison to PBS mice was lower than LT. The soleus was lower in weight in HT mice when compared to PBS mice. TA mass was significantly lower in HT mice when compared to PBS mice. Spleen mass was significantly higher. Fat weight was significantly lower in HT mice when compared to PBS. Atrogin-1 was significantly higher in HT mice when compared to PBS mice. MuRF-1 in HT mice was significantly greater than PBS mice. Ubiquitin HT was significantly greater when compared to PBS and greater than LT. IL-6 was significantly higher in HT mice when compared to PBS mice. Progesterone levels were significantly lower in HT and LT mice when compared to PBS mice. Estrogen levels were significantly lower in HT and LT mice when compared to PBS mice. Conclusions: There appears to be a protective nature in the role of estrogen and progesterone and a negative relationship between these hormones and muscle atrophy. Levels of the E3 ligases Atrogin-1 and MuRF-1 may be elevated in the absence and presence of atrophying muscle and are significantly elevated in atrophic female LLC mice

Hormone Signaling, Gene Expression, and Mitochondrial Hormone Receptor Expression in Avian Muscle (Cells)

Mitochondria are vital to the proper growth and function of muscle cells since they’re responsible for the majority of ATP production used for cellular energy. Previous studies have investigated how differences in mitochondrial function affects feed efficiency (FE) in broilers phenotyped for High and Low FE. Low FE broilers have been shown to have increased levels of reactive oxygen species (ROS), thus contributing to higher levels of oxidative stress and damage seen in these birds. Global gene and protein expression studies conducted on breast muscle of the High FE and Low FE phenotypes have suggested that differences in mitochondrial function and hormone signaling play a role in feed efficiency. In mammalian muscle cells, hormones such as the neuropeptide orexin are known to affect mitochondrial function. Therefore, the focus in this study was to determine whether hormones can affect mitochondrial dynamics in avian muscle cells, compare the expression of genes involved in muscle growth and insulin signaling in the High FE and Low FE phenotypes, and determine whether hormone receptors are present in the mitochondria of avian muscle cells. The actions of hormones and their receptors play an important role in the regulation of growth and metabolism. Investigation of orexin expression in avian muscle cells revealed that the hormone and its receptor are expressed in muscle. Orexin was also shown to be secreted by muscle cells and caused differential expression of a number of mitochondrial-related genes. Based on predictions generated by the results obtained from global expression studies, qRT-PCR analysis revealed several differentially expressed genes between the High and Low FE phenotype that are associated with muscle growth/development and the insulin signaling pathway. Lastly, due to the lack of scientific literature concerning the expression of hormone receptors in the mitochondria of avian muscle cells, studies were conducted that do indicate the presence of receptors in muscle mitochondria

Gene Expression Essential for Myostatin Signaling and Skeletal Muscle Development Is Associated With Divergent Feed Efficiency in Pedigree Male Broilers

Background: Feed efficiency (FE, gain to feed) is an important genetic trait as 70% of the cost of raising animals is due to feed costs. The objective of this study was to determine mRNA expression of genes involved in muscle development and hypertrophy, and the insulin receptor-signaling pathway in breast muscle associated with the phenotypic expression of FE.Methods: Breast muscle samples were obtained from Pedigree Male (PedM) broilers (8 to 10 week old) that had been individually phenotyped for FE between 6 and 7 week of age. The high FE group gained more weight but consumed the same amount of feed compared to the low FE group. Total RNA was extracted from breast muscle (n = 6 per group) and mRNA expression of target genes was determined by real-time quantitative PCR.Results: Targeted gene expression analysis in breast muscle of the high FE phenotype revealed that muscle development may be fostered in the high FE PedM phenotype by down-regulation several components of the myostatin signaling pathway genes combined with upregulation of genes that enhance muscle formation and growth. There was also evidence of genetic architecture that would foster muscle protein synthesis in the high FE phenotype. A clear indication of differences in insulin signaling between high and low FE phenotypes was not apparent in this study.Conclusion: These findings indicate that a gene expression architecture is present in breast muscle of PedM broilers exhibiting high FE that would support enhanced muscle development-differentiation as well as protein synthesis compared to PedM broilers exhibiting low FE

Systematic review of the genetic basis of feed efficiency trait in beef cattle using RNA-Seq studies

30 páginas, ilustraciones, tablas, referencias bibliográficas[ES] El presente trabajo se enfoca en conocer la base genética de la eficiencia alimentaria en el ganado vacuno de carne, considerando su importancia para reducir los costes de nutrición en el sector ganadero, y mitigar el impacto ambiental de la producción animal. La metodología de RNA-Seq ha demostrado ser eficaz para investigar la biología subyacente a este carácter. Sin embargo, los estudios previos en este campo son heterogéneos, dificultando la identificación de genes y rutas metabólicas clave para este fenotipo. Los objetivos de este trabajo son (1) realizar una revisión sistemática de los estudios publicados sobre eficiencia alimentaria en vacuno de carne utilizando RNA-Seq, y (2) contribuir al conocimiento científico integrando los resultados publicados, e identificando genes y procesos biológicos relevantes asociados a este carácter. Como resultado de la revisión sistemática, se identificaron un total de 12 estudios, y 203 candidatos funcionales asociados al carácter eficiencia alimentaria. Entre ellos, los genes MAPK1 y TUBA4A pueden considerarse clave para la eficiencia alimentaria en vacuno de carne, ya que fueron identificados como diferencialmente expresados en cuatro de los artículos revisados. El análisis de enriquecimiento funcional utilizando los 203 genes candidatos, sugieren que la eficiencia alimentaria en el ganado vacuno está asociada con la organización celular, la respuesta a estímulos internos y la regulación de la migración celular, así como con componentes celulares específicos, como los lisosomas y los ribosomas, y vías metabólicas, como la activación y agregación de plaquetas[EN] The present work is focused on understanding the genetic basis of feed efficiency in beef cattle, considering its importance for reducing nutrition costs and mitigating the environmental impact in livestock industry. RNA-Seq methodology has proven effective in investigating the biology underlying this trait. However, previous studies on this trait are heterogeneous, hindering the identification of crucial genes and metabolic pathways for this phenotype. The objectives of this work are (1) to perform a systematic review of published studies on feed efficiency in beef cattle using RNA-Seq, and (2) to contribute to scientific knowledge by integrating published results and identifying relevant genes and biological processes associated with this trait. As a result of the systematic review, a total of 12 studies and 203 functional candidates associated with feed efficiency trait were identified. Among them, MAPK1 and TUBA4A genes can be considered key to feed efficiency in beef cattle, as they were identified as differentially expressed in four reviewed articles. Functional enrichment analyses using the 203 candidate genes suggested that feed efficiency in beef cattle is associated with the cellular organization, response to internal stimuli, and regulation of cell migration, as well as with specific cellular components, such as lysosomes and ribosomes, and metabolic pathways, such as platelet activation and aggregatio

Application of traditional and innovative techniques to investigate productive efficiency and related molecular traits in broiler chickens

Improving feed efficiency represents one of the most important challenges that the poultry industry is currently facing since up to 70% of total production costs is given by feeding. It has been reported that biological limits and animal welfare concerns will limit further genetic improvements of feed efficiency in broiler chickens, strengthening the need for a more detailed comprehension of nutritional and metabolic aspects involved in this trait. Therefore, the present PhD program aimed at evaluating nutritional and physiological aspects involved in overall productivity of broiler chickens, with special regard to feed efficiency, combining both traditional and innovative approaches. In the first trial, it has been shown that the adoption of dietary arginine to lysine ratios higher than those currently recommended had a positive effect on feed efficiency. The analysis of plasma and breast muscle metabolites allowed to hypothesize that these improvements might be ascribed to a modulatory effect of arginine on energy and protein metabolism and hence on overall energy homeostasis. In the second study, productive traits and intestinal transcriptomic profile of two fast-growing chicken hybrids, raised in the same environmental conditions and fed the same diet, were evaluated. The results showed that the genotypes exhibited different growth patterns, feeding behavior, and gene expression profile in the ileum mucosa. Transcriptomic analysis revealed enriched gene sets for mitochondria, cellular energy metabolism, and cell structure and integrity in the first genotype, and enriched gene sets for immune system activation and inflammation in the other one. In conclusion, the results obtained combining both traditional and innovative techniques can shed some light on important aspects involved in productive efficiency of broiler chickens which may allow an optimization of productive strategies to efficiently sustain the increasing demand of poultry meat while improving animal welfare, product quality, and environmental sustainability

Additional file 2: of Progesterone signalling in broiler skeletal muscle is associated with divergent feed efficiency

The qPCR primers used to validate the DE of a subset of genes prioritised by RNAseq. (DOCX 12 kb