Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA275016 | ENA |
REPOSITORIES: ENA
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Project description:The purpose of this study was to examined the acute actions of the second generation antipsychotic (SGA), olanzapine, on skeletal muscle (gastrocnemius) of Sprague Dawley Rats. SGAs cause metabolic side effects including leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. These effects are preceded by glucose intolerance and increased FFA flux and metabolism in peripheral tissues. Skeletal muscle is a likely target of glucose intolerance, therefore understanding how olanzapine affects the skeletal muscle transcriptome could elucidate approaches for mitigating these side effects. Male Sprague-Dawley rats freely fed on normal chow with comparable body weights (vehicle: 373±9g, olanzapine: 388±11g, p=0.34) were infused with vehicle or olanzapine for 24h using a dosing regimen leading to mild hyperglycemia (vehicle, 98±2mg/dl; olanzapine 127±4mg/dl, p=0.0023). For the olanzapine group, the venous catheter was attached to a syringe pump (Model NE-300) filled with olanzapine (Dr. Reddy’s Laboratories Ltd, Hyderabad, India) in sterile saline (infusion: 1mg/100g BW loading dose for 0.5h and then 0.04mg/100g/h continuously for 23.5h). Gastrocnemius was then surgically removed under isoflurane anesthesia (carried with 100% O2), and frozen between two aluminum blocks cooled to the temperature of liquid nitrogen and then stored at -80oC until RNA was isolated. With anesthesia gas flow continuing, the animals were euthanized by cutting the diaphram and removing the heart. The mRNA was isolated from from these muscles and used for RNA-Seq followed by alignment of the data with the rat genome assembly 5.0. To determine significant differences in FPKM values between control and olanzapine groups, the DEGexp function of the DEGseq 1.18.0 R package was used with the Likelihood Ratio Test (LRT) and default parameters. In the uploaded excel file, P values with p<0.05 and p<0.001 are shown for each row in different columns indicated by the number 1. The value 0 indicates the row is not significantly different.
2015-07-17 | GSE65787 | GEO
Project description:To understand the role of LSD1 in transcriptional regulation in muscle under glucocorticoid stress, RNA-seq analyses of gastrocnemius and soleus muscles of skeletal muscle-specific LSD1 KO mice (LSD1-mKO mice) and WT mice after dexamethasone were carried out. We found that LSD1 inhibition led to increased expression of muscle atrophy associated genes and slow fiber genes in gastrocnemius muscle but not in soleus muscle.
2023-01-24 | GSE198826 | GEO
Project description:Title: Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin Sensitivity Abstract: Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1α-/- βf/f/MLC-Cre mice) were generated and characterized. PGC-1α-/-βf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1α- or PGC-1β-deficient mice and wild-type controls. The exercise phenotype of the PGC-1α-/-βf/f/MLC-Cre mice was associated with a marked diminution in muscle oxidative capacity and mitochondrial structural derangements consistent with fusion/fission and biogenic defects together with rapid depletion of muscle glycogen stores during exercise. Surprisingly, the skeletal muscle fiber type profile of the PGC-1α-/-βf/f/MLCCre mice was not significantly different than the wild-type mice. Moreover, insulin sensitivity and glucose tolerance were also not altered in the PGC-1α-/-βf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity. RNA from PGC-1alpha-/- beta f/f/Mlc1fcre was obtained and gene expression pattern compared with PGC-1alpha -/-, PGC-1beta f/f, and PGC-1beta f/f/Mlc1fCre controls. Results file descriptions: 1. GSE23365_skfloxAKO_PPexcl_genesup_GEO-8-16-2010: This table contains genes that were upregulated ≥2.0 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names. 2. GSE23365_skfloxAKO_PPexcl_genesdown_GEO-8-16-2010 This table contains genes that were downregulated ≤0.7 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names.
2010-12-01 | E-GEOD-23365 | biostudies-arrayexpress
Project description:Introduction: The mouse skeletal muscle is composed of four distinct fiber types that differ in contractile function, number of mitochondria and metabolism. Every muscle group has a specific composition and distribution of the four fiber types. Until now, three genes (CnA, PGC1α and PPARδ) are identified that are involved in the generation of more oxidative muscle types. In the present study we searched for novel genes that are involved in specifying different muscle types. Methods: Gastrocnemius and quadriceps muscles were dissected from 20-week old C57BL/6J mice. Gene expression profiles were compared at the level of the whole-transcriptome. The diet-sensitivity of genes differentially expressed between muscle types was explored by comparing mice fed a low fat diet with mice fed a high fat diet. Results: We identified 162 differentially expressed genes in the gastrocnemius as compared with the quadriceps. Genes with the strongest regulations were markers for oxidative fiber types, Hoxd8, Hoxd9 and Hoxd10 and others involved in embryogenesis. Additionally, diet did not influence the expression levels of genes specifying muscle types. Finally, when extrapolating our data to the soleus we could not find a corresponding gene expression pattern between Hoxd8, Hoxd9 and any of the fiber-type specific markers. However, based on these gene expression patterns we could distinguish the gastrocnemius, quadriceps and soleus from each other. Conclusion: Hoxd genes and genes that are markers for the different fiber types specify muscle type in a diet-independent way The aim of the present study was to find novel genes that may play a role in specifying muscle types. Therefore we compared gene expression profiles of the gastrocnemius with the quadriceps at the level of the whole-transcriptome. Functional implications were assessed by the analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways. muscle-type comparison
2010-09-03 | E-GEOD-18127 | biostudies-arrayexpress
Project description:Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples.
| EGAS00001005730 | EGA
Project description:microRNAs responsible for skeletal muscle atrophy are largely unclear. We used microarrays to examine microRNA profiles in rat gastrocnemius muscle of 5 days after denervation of sciatic nerve versus sham control.
2017-08-11 | GSE81914 | GEO
Project description:This study aimed to investigate the effects of glucose restriction (GR) on energy metabolism and muscle fiber type in skeletal muscle. To achieve this goal, we created a mouse model of innate glucose limitation by mutating the major glucose transporter 4 (Glut4) in skeletal muscle. We performed proteomic and phosphoproteomic analyzes of gastrocnemius samples from 12-week-old male Glut4m mice, with or without low-intensity treadmill training.
2023-02-21 | PXD040294 | iProX
Project description:Age-related sarcopenia is associated with a variety of changes in skeletal muscle. These changes are interrelated with each other and associated with systemic metabolism, the details of which, however, are largely unknown. Eicosapentaenoic acid (EPA) is a promising nutrient against sarcopenia and has multifaceted effects on systemic metabolism. Although several human studies have suggested that EPA supplementation protects against sarcopenia, the causal relationship of EPA supplementation and an increase of muscle strength has poor evidence in vivo. We demonstrated that aging skeletal muscle in male mice shows lower grip strength and fiber type changes, both of which can be inhibited by EPA supplementation irrespective of muscle mass alteration. We hypothesized that the aging process in skeletal muscle can be intervened by the administration of EPA, via transcriptomic changes in skeletal muscle. This analysis revealed fast-to-slow fiber type transition in aging muscle, which was partially inhibited by EPA.
2020-12-21 | GSE149307 | GEO
Project description:Adverse effects of statins include skeletal muscle toxicity; Type II glycolytic fibers are more senstive to statin damage; exercise exacerbates statin muscle degeneration. We used a well-characterized rat model of statin-induced muscle degeneration, at which 1.0 mg/kg/day (high dose) cerivastatin produces mild to moderate histological degeneration. We used microarrays to detail the global programme of gene expression underlying cerivastatin effects on rat gastrocnemius and soleus muscles, as well as the effect of cerivastatin combined with treadmill exercise. We identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: We treated female SD rats with vehicle or 3 doses of cerivastatin (0.1, 0.5, 1.0 mg/kg/day) for 14 days, plus or minus 5 days/week of exercise on treadmills (20 min/day at 20 m/min). Gastrocnemius and soleus muscle samples were harvested for RNA extraction and hybridization on Affymetrix microarrays. A total of 12 samples were analyzed with 3-4 biological replicates per sample. Our goals were to determine 1) the effect of cerivastatin; 2) the effect of exercise combined with cerivastatin; 3) an explanation for the muscle fiber type sensitivity to statins. Since all doses of cerivastatin had no effect on soleus muscle (PubMed ID: 16141437), we analysed samples from soleus from control and high dose groups only.
2008-06-13 | E-GEOD-4418 | biostudies-arrayexpress
Project description:Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle fiber proteins that associate with Gadd45a as it induces skeletal muscle atrophy in living mice. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, the MAP kinase kinase kinase MEKK4. Furthermore, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into way that skeletal muscle atrophy occurs at the molecular level.
2016-05-17 | MSV000079730 | MassIVE