Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA196841 | ENA |
REPOSITORIES: ENA
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Project description:In the present study, we conducted transcriptomics on skeletal muscle from 6-month-old UCP1 KI and wild-type (WT) pigs to explore the transcriptional programs induced by adipocyte-specific UCP1 overexpression in skeletal muscle
2022-02-02 | GSE189334 | GEO
Project description:Aged skeletal muscle is markedly affected by fatty muscle infiltration and strategies to reduce the occurrence of adipocytes within skeletal muscle, the intramuscular adipose tissue (IMAT), are urgently needed. Fibroblast growth factor-2 (FGF-2) is a critical growth factor for muscle tissue. Here, we show that FGF-2 not only stimulates muscle growth, but also promotes intramuscular adipogenesis. Using multiple screening assays for upstream and downstream signaling of microRNA (miR)-29a we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle from aged mice. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1 which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and AAV-mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular fat formation in vivo. Thus, our data highlight an ambivalent role of FGF-2 for adult skeletal muscle and reveal a novel pathway to combat fat accumulation in aged skeletal muscle.
2021-08-23 | PXD020575 | Pride
Project description:To determine the effects of cold exposure on skeletal muscle gene expression in rats with and without UCP1, we assessed gastrocnemius muscle in chow-fed control and whole body UCP1 knockout rats using RNA-seq.
2022-03-01 | GSE171814 | GEO
Project description:To determine the transcriptomic effects of cold exposure on skeletal muscle gene expression in rats with and without UCP1, we assessed gastrocnemius muscle in chow-fed control and whole body UCP1 knockout rats using RNA-seq.
2022-06-01 | GSE176507 | GEO
Project description:Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPH-generating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stress-signaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.-Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K.-J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., and Klaus, S. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. Control C57BL/6J wildtype male mice, aged 12 weeks, are compared to UCP1 transgene littermates fed purified low fat diet (BIOCLAIMS, Hoevenaars et al., Genes and Nutrition 2012) for 12 weeks . At the end, mice were sacrificed, gastrocnemius skeletal muscle was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 8x60K microarrays. In total, 6 arrays of individual WT and 7 arrays of individual UCP1-TG samples were normalized, together with samples from the complete SUPERSERIES.
2015-02-17 | E-GEOD-45991 | biostudies-arrayexpress
Project description:Skeletal muscle is not only a primary site for glucose uptake and storage, but also a reservoir for amino acids stored as protein. How the metabolism of these two fuels is coordinated in skeletal muscle is incompletely understood. Here, we demonstrate that interferon regulatory factor 4 (IRF4) integrate glucose and amino acids flux by regulating glycogen synthesis and branched-chain-amino acid (BCAA) metabolism in skeletal muscle. Mice with IRF4 specifically knocked out in skeletal muscle (MI4KO) showed elevated plasma BCAAs and skeletal muscle glycogen content, decreased adiposity and body weight, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity (DIO). Loss of IRF4 caused downregulation of the mitochondrial branched-chain aminotransferase isozyme (BCATm) in myocytes, which encodes for the enzyme catalyzing the first step of BCAA metabolism. Lack of IRF4 also led to the upregulation of protein targeting to glycogen (PTG), which is associated with enhanced mitochondrial Complex II activity and mitochondria number. Additionally, overexpression of IRF4 in skeletal muscle caused obesity and reduced exercise capacity. Mechanistically, we found that IRF4 directly regulates both BCATm and PTG expression, and that overexpression of BCATm can partially reverse the effects of IRF4 deletion. These studies establish IRF4 as a novel driver of both glucose and BCAA metabolism in skeletal muscle.
2019-08-30 | GSE136623 | GEO
Project description:Androgens act through androgen receptor (AR) to maintain muscle mass. Evidence suggests that this pathway is influenced by ACTN3 (α-actinin-3) - “the Gene for Speed”. Given that one in 5 people worldwide lack α-actinin-3, it is possible they may respond to androgens differently. In this study, we show that α-actinin-3 deficiency decreases AR in skeletal muscles of mice and humans (in males and females), and that AR levels positively correlate with α-actinin-3 expression in a dosage dependent manner. α-Actinin-3 deficiency exacerbates gastrocnemius muscle mass loss with androgen deprivation in male mice, and stunts the muscle growth response to dihydrotestosterone at the onset of puberty in female mice. This is mediated by differential activation of pathways regulating amino acid metabolism, intracellular transport, autophagy, mitochondrial activity, MAPK and calcineurin signalling, which may be driven by 7 key genes that are both androgen sensitive and α-actinin-3-dependent in expression. Our results highlight a role for α-actinin-3 in the regulation of muscle mass and suggest that ACTN3 is a genetic modifier of androgen action in skeletal muscle.
2025-08-01 | GSE299080 | GEO
Project description:BACKGROUND: Histone deacetylase 4 (HDAC4) has been proposed as a target for the treatment of Amyotrophic Lateral Sclerosis (ALS) because it mediates nerve-skeletal muscle interaction and since its expression in skeletal muscle correlates with the severity of the disease. However, our recent studies on the skeletal muscle response upon long-term denervation highlighted the importance of HDAC4 in maintaining muscle integrity. METHODS: To fully identify the yet uncharacterized HDAC4 functions in ALS, we genetically deleted HDAC4 in skeletal muscles of a mouse model of ALS. Body weight, skeletal muscle, innervation and spinal cord were analyzed over time by morphological and molecular analyses. A transcriptome analysis was also performed to delineate the signaling modulated by HDAC4 in skeletal muscle of a mouse model of ALS. FINDINGS: HDAC4 deletion in skeletal muscle caused earlier ALS onset, characterized by body weight loss, muscle denervation and atrophy, and compromised muscle performance in ALS mice, although the main catabolic pathways were not activated. A transcriptome analysis identified the gene networks modulated by HDAC4 in ALS, revealing UCP1 as a top regulator that may be implicated in worsening ALS features. INTERPRETATION: HDAC4 plays an important role in preserving innervations and skeletal muscle in ALS, likely by modulating the UCP1 gene network. Our study highlights a possible risk in considering HDAC inhibitors for the treatment of ALS.
2019-01-31 | GSE121789 | GEO
Project description:Skeletal muscles undergo atrophy in response to denervation and neuromuscular diseases. Understanding the mechanisms by which denervation drives muscle atrophy is crucial for developing therapies against neurogenic muscle atrophy. Here, we identify muscle-secreted fibroblast growth factor 21 (FGF21) as a key inducer of atrophy following muscle denervation. In denervated skeletal muscles, Fgf21 is the most robustly upregulated member of the Fgf family and acts in an autocrine/paracrine manner to promote muscle atrophy. Silencing Fgf21 in muscle prevents denervation-induced muscle wasting by preserving neuromuscular junction (NMJ) innervation. Conversely, forced expression of FGF21 in muscle reduces NMJ innervation, leading to muscle atrophy. Mechanistically, TGFB1 released by denervated fibro-adipogenic progenitors (FAPs) upregulates Fgf21 through the JNK/c-Jun axis. The resulting increase in FGF21 protein reduces the cytoplasmic level of histone deacetylase 4 (HDAC4), culminating in muscle atrophy. HDAC4 knockdown abolishes the atrophy-resistant effects observed in Fgf21-deficient denervated muscles, resulting in muscle atrophy. Our findings reveal a novel role and heretofore unrecognized mechanism of FGF21 in skeletal muscle atrophy, suggesting that inhibiting muscular FGF21 could be a promising strategy for mitigating skeletal muscle atrophy.
2025-11-06 | GSE303861 | GEO
Project description:It is well established that obese animals and humans show deficiencies in skeletal muscle content and metabolism. However, the mechanisms under how skeletal muscle metabolism affects systemic energy homeostasis is not well-defined. Here, we compared the skeletal muscle transcriptome from obese and lean controls in different species. We found an immune-responsive transcription factor interferon regulatory factor 4 (IRF4) was conserved to be increased in obese subjects from the three species (humans, non-human primates and mice). Thus, we demonstrated that loss of IRF4 specifically in skeletal muscle of mice showed protection against the metabolic effects of high-fat diet, with unexpected increased plasma and muscle branched-chain amino acid (BCAA) levels. Conversely, overexpression of skeletal muscle IRF4 caused obesity and insulin resistance, with decreased BCAA contents. Mechanistically, IRF4 can transcriptionally regulate branched-chain aminotransferase isozyme (BCATm) expression, and that overexpression of BCATm can reverse the effects of IRF4 depletion regarding to metabolic phenotypes. Further, we demonstrated ablation of IRF4 in skeletal muscle increased mitochondrial activity and glycogen synthesis in a BCATm- dependent manner. These studies establish IRF4 as a novel driver of BCAA metabolism via BCATm in skeletal muscle and may interpret the BCAAs paradox in obesity.
2024-07-29 | GSE181107 | GEO