Upstream Regulator Analysis of Wooden Breast Myopathy Proteomics in Commercial Broilers and Comparison to Feed Efficiency Proteomics in Pedigree Male Broilers

Abstract

In an effort to understand the apparent trade-off between the continual push for growth performance and the recent emergence of muscle pathologies, shotgun proteomics was conducted on breast muscle obtained at ~8 weeks from commercial broilers with wooden breast (WB) myopathy and compared with that in pedigree male (PedM) broilers exhibiting high feed efficiency (FE). Comparison of the two proteomic datasets was facilitated using the overlay function of Ingenuity Pathway Analysis (IPA) (Qiagen, CA, USA). We focused on upstream regulator analysis and disease-function analysis that provides predictions of activation or inhibition of molecules based on (a) expression of downstream target molecules, (b) the IPA scientific citation database. Angiopoeitin 2 (ANGPT2) exhibited the highest predicted activation Z-score of all molecules in the WB dataset, suggesting that the proteomic landscape of WB myopathy would promote vascularization. Overlaying the FE proteomics data on the WB ANGPT2 upstream regulator network presented no commonality of protein expression and no prediction of ANGPT2 activation. Peroxisome proliferator coactivator 1 alpha (PGC1α) was predicted to be inhibited, suggesting that mitochondrial biogenesis was suppressed in WB. PGC1α was predicted to be activated in high FE pedigree male broilers. Whereas RICTOR (rapamycin independent companion of mammalian target of rapamycin) was predicted to be inhibited in both WB and FE datasets, the predictions were based on different downstream molecules. Other transcription factors predicted to be activated in WB muscle included epidermal growth factor (EGFR), X box binding protein (XBP1), transforming growth factor beta 1 (TGFB1) and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2). Inhibitions of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT) and estrogen related receptor gamma (ESRRG) were also predicted in the WB muscle. These findings indicate that there are considerable differences in upstream regulators based on downstream protein expression observed in WB myopathy and in high FE PedM broilers that may provide additional insight into the etiology of WB myopathy.

Proteomic analyses on chicken breast meat with white striping myopathy

“…Previously, a shotgun proteomics study, which was conducted with WS and WB co-affected muscles ( WS/WB ) collected at ∼5 min postmortem compared with normal muscles, showed potentially altered physiological mechanisms, including carbohydrate metabolism, protein synthesis, oxidative stress and mitochondrial dysfunctions ( Kuttappan et al, 2017 ; Bottje et al, 2021 ). When compared differentially abundant proteins of WS only muscle collected at 6 h postmortem (WS-6h) in this study with those in WS/WB muscles collected at ∼5 min postmortem (WS/WB-5min) in the previous study, proteins showing the same differential trends may reflect similar protein stabilities between WS and normal meat during processing procedures and short-term storage.…”

“…Weighted gene co-expression network analysis ( WGCNA ) based on gene expression profiles obtained with WB and WS muscles suggested that alterations in extracellular matrix composition could activate the growth-related myopathies onset, and that collagen IV alterations may induce the endoplasmic reticulum stress response ( Bordini et al, 2021 ). Proteomics studies with severe WB and WS muscles identified differentially expressed proteins associated with increased protein synthesis, decreased carbohydrate metabolic activity, decreased mitochondrial biogenesis, and reduced function of rapamycin independent companion of mammalian target of rapamycin ( RICTOR ) ( Bottje et al, 2021 ; Kuttappan et al, 2017 ). However, global protein expression studies on WS-only muscle phenotype without other breast myopathy were limited in contrast to a variety of omics studies on WB (and WB with WS).…”

Thigh muscle metabolic response is linked to feed efficiency and meat characteristics in slow-growing chicken

“…In addition to glycolysis/gluconeogenesis and the protein-synthesizing pathways that were identified, mitochondrial activity has previously been reported to be among the most significant pathways influencing FE ( Bottje et al, 2002 ; Kong et al, 2016 ; Yang et al, 2020 ) and meat quality ( Abaht et al, 2019 ; Bottje et al, 2021 ). Mitochondria function is critical for improving FE due to its potential role in generating and utilizing energy extracted from feed ( Bottje et al, 2006 ).…”

Multi-Omics Analysis of the Microbiome and Metabolome Reveals the Relationship Between the Gut Microbiota and Wooden Breast Myopathy in Broilers

“…Rather than adding myofibers, muscles grow longitudinally through the accretion of myoblasts, resulting in an increasing pool of myonuclei, which regulate the addition of sarcomeric units and skeletal muscle growth ( 44 , 45 ). Intense selection for growth performance in broilers causes an excessive rate of breast muscle growth ( 46 ), which may favor more vulnerable myofibers. After the occurrence of myofiber injury, monocytes invade and remove necrotic cells and cellular debris ( 47 ).…”