Display omitted
•Variation in metabolome due to sampling position in muscle.•Changes in metabolome due to aging are more pronounced than position effect.•Eleven biomarkers for aging time ...applied.•Four biomarkers for aging type applied.
The aging of beef affects the metabolome and, thus, its quality, such as taste or tenderness. In addition to the aging method, intrinsic factors, such as breed, feed and muscle type, also have an effect on beef’s metabolome. It is not known yet whether the position of the sampling in large muscles also has an influence on beef’s metabolome and its aging outcome. The effect of the sampling position in M. longissimus dorsi as a large muscle was investigated in dry-aged and wet-aged beef over an aging period of 28 days. In this study, we analyzed 360 samples out of the entire length of M. longissimus dorsi of 18 ‘Simmental’ young bulls by 1H NMR spectroscopy. The position in the muscle affected the polar fraction of metabolome of non-aged and aged beef significantly. However, sampling position did not overlay significant differences in the metabolome of dry-aged and wet-aged beef. The aging time of beef also had a significant effect on the metabolome. Marker metabolites, such as leucine, isoleucine, inosine 5′-monophosphate and hypoxanthine, were found to be indicative of the aging time applied. In addition, marker metabolites (lactic acid, anserine, O-acetyl-L-carnitine) were identified for the aging type applied.
Farm animal skeletal muscle, formed through development, growth, and maturation processes, is converted to edible meat during postmortem rigor mortis and aging. Live and postmortem muscle metabolism ...is the phenotypic determinant of muscle characteristics and meat quality traits such as flavor and color. Meanwhile, animal muscle metabolism, originally programmed by genetic program, is modulated by feeding and environmental conditions through changes in the biosynthetic network. Metabolomics deepens our understanding of metabolisms underlying skeletal muscle growth, maturation, abnormality, and postmortem meat aging. The metabolomics approach is beneficial to explore biomarkers to monitor meat production processes and products, leading to improvements in livestock productivity and meat quality. One of the recent metabolomics findings in animal muscle could be the impact of mitochondrial activity and energy metabolisms on meat quality. The present review overviews the advances in metabolomics studies of farm animal skeletal muscle, to gain an insight into the muscle metabolisms associated with livestock production and meat quality.
•Skeletal muscle metabolism is altered by genetic background, feeding, and postmortem aging.•Molecular events in both live and postmortem muscle affect quality and productivity of meat.•Metabolomics combined with bioinformatics is a powerful tool to elucidate muscle metabolism.•Mitochondrial function and redox metabolism have a large impact on meat quality.
Despite abundant knowledge of the regulation and biochemistry of glycolytic enzymes, we have limited understanding on how they are spatially organized in the cell. Emerging evidence indicates that ...nonglycolytic metabolic enzymes regulating diverse pathways can assemble into polymers. We now show tetramer- and substrate-dependent filament assembly by phosphofructokinase-1 (PFK1), which is considered the "gatekeeper" of glycolysis because it catalyzes the step committing glucose to breakdown. Recombinant liver PFK1 (PFKL) isoform, but not platelet PFK1 (PFKP) or muscle PFK1 (PFKM) isoforms, assembles into filaments. Negative-stain electron micrographs reveal that filaments are apolar and made of stacked tetramers oriented with exposed catalytic sites positioned along the edge of the polymer. Electron micrographs and biochemical data with a PFKL/PFKP chimera indicate that the PFKL regulatory domain mediates filament assembly. Quantified live-cell imaging shows dynamic properties of localized PFKL puncta that are enriched at the plasma membrane. These findings reveal a new behavior of a key glycolytic enzyme with insights on spatial organization and isoform-specific glucose metabolism in cells.
Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to ...disease. At present, the full set of molecular mechanisms governing the relative expression and balance of these two pathways is unknown. Here, we focus on genes whose loss leads to an increase in OXPHOS activity. Unexpectedly, this class of genes is enriched for components of the pre-mRNA splicing machinery, in particular for subunits of the U1 snRNP. Among them, we show that LUC7L2 represses OXPHOS and promotes glycolysis by multiple mechanisms, including (1) splicing of the glycolytic enzyme PFKM to suppress glycogen synthesis, (2) splicing of the cystine/glutamate antiporter SLC7A11 (xCT) to suppress glutamate oxidation, and (3) secondary repression of mitochondrial respiratory supercomplex formation. Our results connect LUC7L2 expression and, more generally, the U1 snRNP to cellular energy metabolism.
Display omitted
•Expression of LUC7L2 and the U1 snRNP represses OXPHOS•Pre-mRNA splicing and expression of PFKM and SLC7A11 (xCT) requires LUC7L2•Loss of LUC7L2 and glycolysis promotes respiratory chain (super)complex assembly•LUC7 family members cross-regulate each other's expression
Jourdain et al. report the identification of OXPHOS repressors, genes whose loss shifts metabolism from glycolysis to OXPHOS. Prominent in this set are members of the U1 snRNP, including LUC7L2. The authors show that loss of LUC7L2 leads to metabolic crossovers at PFKM and SLC7A11 (xCT), thereby impacting glycogen formation and glutamate oxidation.
Renal fibrosis is a common pathological feature and outcome of almost all chronic kidney diseases, and it is characterized by metabolic reprogramming toward aerobic glycolysis. Mesenchymal stem ...cell-derived exosomes (MSC-Exos) have been proposed as a promising therapeutic approach for renal fibrosis. In this study, we investigated the effect of MSC-Exos on glycolysis and the underlying mechanisms. We demonstrated that MSC-Exos significantly ameliorated unilateral ureter obstruction (UUO)-induced renal fibrosis by inhibiting glycolysis in tubular epithelial cells (TECs). miRNA sequencing showed that miR-21a-5p was highly enriched in MSC-Exos. Mechanistically, miR-21a-5p repressed the expression of phosphofructokinase muscle isoform (PFKM), a rate-limiting enzyme of glycolysis, thereby attenuating glycolysis in TECs. Additionally, knockdown of miR-21a-5p abolished the renoprotective effect of MSC-Exos. These findings revealed a novel role for MSC-Exos in the suppression of glycolysis, providing a new insight into the treatment of renal fibrosis.
The extrahypothalamic growth hormone-releasing hormone (GHRH) and its cognate receptors (GHRH-Rs) and splice variants are expressed in a variety of cancers. It has been shown that the pituitary type ...of GHRH-R (pGHRH-R) mediates the inhibition of tumor growth induced by GHRH-R antagonists. However, GHRH-R antagonists can also suppress some cancers that do not express pGHRH-R, yet the underlying mechanisms have not been determined. Here, using human esophageal squamous cell carcinoma (ESCC) as a model, we were able to reveal that SV1, a known splice variant of GHRH-R, is responsible for the inhibition induced by GHRH-R antagonist MIA-602. We demonstrated that GHRH-R splice variant 1 (SV1) is a hypoxia-driven promoter of tumor progression. Hypoxia-elevated SV1 activates a key glycolytic enzyme, muscle-type phosphofructokinase (PFKM), through the nuclear factor kappa B (NF-κB) pathway, which enhances glycolytic metabolism and promotes progression of ESCC. The malignant actions induced by the SV1–NF-κB–PFKM pathway could be reversed by MIA-602. Altogether, our studies demonstrate a mechanism by which GHRH-R antagonists target SV1. Our findings suggest that SV1 is a hypoxia-induced oncogenic promoter which can be an alternative target of GHRH-R antagonists.
•Mitochondrial dysfunction occurred in two different pork muscles during aging.•Cytochrome c was released and caspase-3 was activated in both muscle types.•PM exhibited higher apoptotic potential ...compared to LD.•PM showed lower myofibrillar proteolysis than LD.•Apoptosis-mediated proteolysis could be muscle-specific.
This study aims to investigate the changes in mitochondrial apoptotic factors and proteolysis of two porcine muscles (psoas major – PM and longissimus dorsi – LD) during aging. Results found that during 2–168 h postmortem mitochondrial membrane permeability, mitochondrial lipid peroxidation, Ca2+ levels were increased, while the reduction level and abundance of cytochrome c were decreased (P < 0.05) in both muscle types. Furthermore, the activation of caspase-3 along with increases in troponin-T and desmin degradation, and μ-calpain autolysis were found (P < 0.05), regardless of muscle type. PM maintained higher mitochondrial apoptotic factors, but had more intact desmin, less troponin-T degradation and less extent of autolyzed products of μ-calpain compared to LD (P < 0.05). These results indicate that the rapid onset of mitochondrial apoptosis of PM would not lead to a subsequent impact on myofibrillar protein degradation, suggesting that the mitochondrial apoptosis mediated tenderization process could be muscle-specific.
Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract. The loss and gain of miRNA function promote cancer development through various mechanisms. RNA ...sequencing (RNA-seq) and miRNAs sequencing data from the Cancer Genome Atlas (TCGA) was used to show the dysfunctional miRNAs microenvironment and to provide useful biomarkers for miRNAs therapy. Seven miRNAs were found to be independent prognostic factors of HNSCC patients in the training cohort. A total of 60 target genes for these miRNAs were predicted. Nine target genes (CDCA4, CXCL14, FLNC, KLF7, NBEAL2, P4HA1, PFKM, PFN2 and SEPPINE1) were correlated with patient's overall survival (OS) outcomes. We identified novel miRNAs markers for the prognosis of head and neck squamous cell carcinoma.
•The loss and gain of miRNA function promote cancer development through various mechanisms in HNSCC.•Seven miRNAs were found to be independent prognostic factors of HNSCC patients.•A prognosis signature based on miRNAs markers was constructed in HNSCC.
Phosphofructokinase-M (PFKM) is a key enzyme in glycolysis. The expression and activity of PFKM is closely related to the occurrence and development of malignant tumors, but its role in the ...regulation of renal cell carcinoma (RCC) is still unknown. We found that the expression of PFKM was lower in RCC tumor tissue than in adjacent normal tissues, and that low expression of PFKM was related to the poor overall survival of RCC patients. In addition, our results showed that FOXO3 mediated PFKM inhibited the growth, migration and invasion of RCC cells, suggesting that PFKM is a protective factor for RCC.
•PFKM expression is down-regulated in renal cell carcinoma.•Patients with low PFKM expression have poorer overall survival.•PFKM mRNA and protein expression levels are downregulated in patient tissues.•PFKM overexpression inhibits RCC proliferation, migration, and invasion, and induces S phase arrest.•FOXO3 is needed for PFKM-induced inhibition of RCC proliferation.
The objective of this study was to assess the meat quality in second filial hybrid offspring of MSTN−/− cloning boars × Chinese Bama sows with initial mean body weight of 90.52 ± 0.68 kg. Compared ...with wild-type pigs, the feed utilization rate of MSTN−/− pigs showed an increasing trend (adjusted P = 0.06), loin eye area of MSTN−/− and MSTN+/− pigs increased (adjusted P < 0.01) and thickness of subcutaneous fat decreased (adjusted P < 0.01), the proportion of polyunsaturated fatty acids in meat of MSTN−/− pigs increased (adjusted P < 0.05). By means of histochemical staining, immunofluorescence, scanning electron microscopy, qRT-PCR and WB technologies, it was verified that the decreased meat color score of MSTN−/− pigs was related to the increase of type IIB muscle fiber, and the increased pork tenderness was related to the decrease of collagen content. Overall, this research provides reference for the further utilization of MSTN gene mutant pigs.
•Meat color score of MSTN−/− pig (F2) is lower, due to the increase of the proportion of type IIB muscle fibers.•Longissimus thoracis muscle of MSTN−/− pig (F2) has lower fat content and higher proportion of polyunsaturated fatty acid.•Meat of MSTN−/− pig (F2) is more tender, because of the decrease of collagen content.
PDF
