Gene Expression Levels In Muscle Research Articles

Identification of genomic regions, genetic variants and gene networks regulating candidate genes for lipid metabolism in pig muscle

The intramuscular fat content and fatty acid composition of porcine meat have a significant impact on its quality and nutritional value. This research aimed to investigate the expression of 45 genes involved in lipid metabolism in the longissimus dorsi muscle of three experimental pig backcrosses, with a 25% of Iberian background. To achieve this objective, we conducted an expression Genome-Wide Association Study (eGWAS) using gene expression levels in muscle measured by high-throughput real-time qPCR for 45 target genes and genotypes from the PorcineSNP60 BeadChip or Axiom Porcine Genotyping Array and 65 single nucleotide polymorphisms (SNPs) located in 20 genes genotyped by a custom-designed Taqman OpenArray in a cohort of 354 animals. The eGWAS analysis identified 301 eSNPs associated with 18 candidate genes (ANK2, APOE, ARNT, CIITA, CPT1A, EGF, ELOVL6, ELOVL7, FADS3, FASN, GPAT3, NR1D2, NR1H2, PLIN1, PPAP2A, RORA, RXRA and UCP3). Three cis-eQTL (expression quantitative trait loci) were identified for GPAT3, RXRA, and UCP3 genes, which indicates that a genetic polymorphism proximal to the same gene is affecting its expression. Furthermore, 24 trans-eQTLs were detected, and eight candidate regulatory genes were located in these genomic regions. Additionally, two trans-regulatory hotspots in Sus scrofa chromosomes 13 and 15 were identified. Moreover, a co-expression analysis performed on 89 candidate genes and the fatty acid composition revealed the regulatory role of four genes (FABP5, PPARG, SCD, and SREBF1). These genes modulate the levels of α-linolenic, arachidonic, and oleic acids, as well as regulating the expression of other candidate genes associated with lipid metabolism. The findings of this study offer novel insights into the functional regulatory mechanism of genes involved in lipid metabolism, thereby enhancing our understanding of this complex biological process.

Comparisons of adipogenesis- and lipid metabolism-related gene expression levels in muscle, adipose tissue and liver from Wagyu-cross and Holstein steers.

The intramuscular fat (IMF) content and fatty acid composition are important meat quality traits that are mostly affected by the cattle breed. Muscle, adipose tissue and liver are important organs involved in the development of intramuscular adipose tissue. Thus, we hypothesized that there were marked differences in the adipogenesis and lipid metabolism of these tissues between Wagyu-cross and Holstein steers during the finishing phases. To test this hypothesis, we analyzed the expression levels of adipogenesis- and lipid metabolism-related genes in longissimus muscle (LM), subcutaneous fat (SCF) and liver from Wagyu-cross and Holstein steers at 26 months of age. The IMF content and fatty acid profile of LM were determined. Wagyu-cross steers had a higher IMF content and MUFA percentages in the LM than Holstein steers (P<0.05). The relative expression of FGF2, COL1A1, SREBP1c, SCD1, GRP78 and LEP was greater in the LM of Wagyu-cross steers than in Holstein steers (P<0.05). In contrast, Holstein steer SCF had higher (P<0.05) mRNA expression levels of FABP4 and ADIPOQ than Wagyu-cross steers. In the liver, the expression of SREBP1c and GRP78 in Wagyu-cross steers was significantly higher than that in Holstein steers (P<0.05). The results demonstrate that both intramuscular adipogenesis and fibrogenesis are enhanced in Wagyu-cross steers compared with Holstein steers during the finishing phase and that IMF deposition is positively correlated with the maturity of SCF and hepatic lipid accumulation in Wagyu-cross steers.

Cerebral Palsy and Stroke—Early and Late Brain Lesion Present Differences in Systemic Biomarkers and Gene Expression Related to Muscle Contractures

Background: CNS lesions that are acquired early in life e.g. cerebral palsy (CP) disturb muscle development and growth, while CNS injuries acquired later in life e.g. stroke, affect fully matured muscles and cause paresis and atrophy. These differences may result in different contracture phenotypes. Aim: The purpose of this study was to compare systemic biomarkers and gene expression levels in muscle of individuals with CNS lesions acquired early and later in life. Methods: Blood samples and muscle biopsies were analyzed using Enzyme-linked immunosorbent assay and Real-time PCR from n = 24 control participants, n = 14 individuals with cerebral palsy, and n = 12 stroke survivors. Results: Systemic markers: Myostatin was significantly decreased in both the cerebral palsy (p = 0.0051), and the stroke group (p = 0.036). Creatine Kinase-MB and C-Reactive Protein were significantly elevated in stroke patients only (p 0.034 respectively). Gene expressions: The expression of myostatin (MSTN) was significantly lower in both the ST and the CP group when compared to Ctrl (p = 0.02). In addition, collagen type 4A1 (COL4A1) was significantly lower in the CP group compared to the other groups (p = 0.015). Finally, the troponin 1 slow skeletal muscle type was significantly increased in the ST group when compared to both CP and Ctrl (p = 0.03). Conclusion: The downregulation of myostatin in individuals with both early and late CNS injury is likely a compensatory reaction to muscle weakness, reduced muscle mass and/or muscle atrophy. Changes in gene expression may reflect a specific alteration depending on when in life the CNS lesions were acquired.

Endurance Runners with Intramyocellular Lipid Accumulation and High Insulin Sensitivity Have Enhanced Expression of Genes Related to Lipid Metabolism in Muscle.

Context: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. Design and setting: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic–hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. Results: IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, “RESPONSE TO LIPID” was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2–3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. Conclusions: Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle.

Effects of blood flow restriction on muscle size and gene expression in muscle during immobilization: A pilot study.

PurposeMuscle mass is known to rapidly decrease with muscle disuse. Previous reports suggest that repetitive blood flow restriction (BFR) mitigates the reduction of muscle mass with disuse. However, the effects of BFR on muscle atrophy and gene expression levels in muscle during cast immobilization have not been clarified.MethodsTo investigate the effect of BFR on muscle atrophy and gene expression levels during cast immobilization in humans, we recruited 10 healthy males who were randomly divided into the control and BFR treatment groups. All subjects were immobilized with a cast for 14 days. BFR treatment was conducted only in the BFR group. We evaluated cross sectional area (CSA) of thigh muscles by magnetic resonance imaging before and 14 days after cast immobilization. A percutaneous biopsy of the vastus lateralis muscle (VL) was performed before and 1, 7, and 14 days after cast immobilization. Expression of genes related to muscle atrophy and synthesis were evaluated using real‐time PCR.ResultsThe CSA of the VL and the thigh flexor muscles were significantly decreased in both groups; however, percent decrease in CSA was significantly smaller in the BFR group compared with the control group. In two‐way repeated ANOVA analysis, the time × treatment interaction in gene expression of the muscle‐specific ubiquitin ligases muscle ring finger 1 (MuRF1) was significant, and elevated MURF1 expression level by cast immobilization was seemed to be suppressed by the BFR treatment.ConclusionBFR treatment may prevent reduced VL and thigh flexor muscles and increased MuRF1 expression level during cast immobilization. Further study is required to confirm these results.

Exploring the underlying biology of intrinsic cardiorespiratory fitness through integrative analysis of genomic variants and muscle gene expression profiling.

Intrinsic cardiorespiratory fitness (CRF) is defined as the level of CRF in the sedentary state. There are large individual differences in intrinsic CRF among sedentary adults. The physiology of variability in CRF has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were explored in the present study by interrogating intrinsic CRF-associated DNA sequence variation and skeletal muscle gene expression data from the HERITAGE Family Study through an integrative bioinformatics guided approach. A combined analytic strategy involving genetic association, pathway enrichment, tissue-specific network structure, cis-regulatory genome effects, and expression quantitative trait loci was used to select and rank genes through a variation-adjusted weighted ranking scheme. Prioritized genes were further interrogated for corroborative evidence from knockout mouse phenotypes and relevant physiological traits from the HERITAGE cohort. The mean intrinsic V̇o2max was 33.1 ml O2·kg-1·min-1 (SD = 8.8) for the sample of 493 sedentary adults. Suggestive evidence was found for gene loci related to cardiovascular physiology (ATE1, CASQ2, NOTO, and SGCG), hematopoiesis (PICALM, SSB, CA9, and CASQ2), skeletal muscle phenotypes (SGCG, DMRT2, ADARB1, and CASQ2), and metabolism (ATE1, PICALM, RAB11FIP5, GBA2, SGCG, PRADC1, ARL6IP5, and CASQ2). Supportive evidence for a role of several of these loci was uncovered via association between DNA variants and muscle gene expression levels with exercise cardiovascular and muscle physiological traits. This initial effort to define the underlying molecular substrates of intrinsic CRF warrants further studies based on appropriate cohorts and study designs, complemented by functional investigations. NEW & NOTEWORTHY Intrinsic cardiorespiratory fitness (CRF) is measured in the sedentary state and is highly variable among sedentary adults. The physiology of variability in intrinsic cardiorespiratory fitness has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were explored computationally in the present study, with further corroborative evidence obtained from analysis of phenotype data from knockout mouse models and human cardiovascular and skeletal muscle measurements.

Self-Crosslinking Lipopeptide/DNA/PEGylated Particles: A New Platform for DNA Vaccination Designed for Assembly in Aqueous Solution

Delivery of plasmids for gene expression in vivo is an inefficient process that requires improvement and optimization to unlock the clinical potential of DNA vaccines. With ease of manufacture and biocompatibility in mind, we explored condensation of DNA in aqueous solution with a self-crosslinking, endosome-escaping lipopeptide (LP), stearoyl-Cys-His-His-Lys-Lys-Lys-amide (stearoyl-CH2K3), to produce cationic LP/DNA complexes. To test whether poly(ethylene glycol) (PEG)-ylation of these cationic complexes to neutralize the surface charge would improve the distribution, gene expression, and immune responses poly(ethylene glycol), these LP/DNA complexes were combined with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). Fluorescence imaging illustrated that the cationic complexes exhibited the highest degree of localization and lowest degree of dispersion throughout the injected muscle, suggesting impaired mobility of cationic particles upon administration. Nanoluciferase reporter assays over a 90-day period demonstrated that gene expression levels in muscle were highest for PEGylated particles, with over a 200-fold higher level of expression than the cationic particles observed at 30 days. Humoral and cell-mediated immune responses were evaluated in vivo after injection of an ovalbumin expression plasmid. PEGylation improved both immune responses to the DNA complexes in mice. Overall, this suggests that PEGylation of cationic lipopeptide complexes can significantly improve both the transgene expression and immunogenicity of intramuscular DNA vaccines.

Phenotypic plasticity in gene expression contributes to divergence of locally adapted populations of Fundulus heteroclitus.

We examine the interaction between phenotypic plasticity and evolutionary adaptation using muscle gene expression levels among populations of the fish Fundulus heteroclitus acclimated to three temperatures. Our analysis reveals shared patterns of phenotypic plasticity due to thermal acclimation as well as non-neutral patterns of variation among populations adapted to different thermal environments. For the majority of significant differences in gene expression levels, phenotypic plasticity and adaptation operate on different suites of genes. The subset of genes that demonstrate both adaptive differences and phenotypic plasticity, however, exhibit countergradient variation of expression. Thus, expression differences among populations counteract environmental effects, reducing the phenotypic differentiation between populations. Finally, gene-by-environment interactions among genes with non-neutral patterns of expression suggest that the penetrance of adaptive variation depends on the environmental conditions experienced by the individual.