Ten-day human unilateral lower limb suspension and active recovery in young healthy men
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE211204 | GEO | 2022/09/27
REPOSITORIES: GEO
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Project description:Skeletal muscle unloading due to joint immobilization induces skeletal muscle atrophy. However, the skeletal muscle proteome response to limb immobilization has not been investigated using SWATH methods. This study quantitatively characterized the muscle proteome at baseline, and after 3 and 14 d of unilateral lower limb (knee-brace) immobilization in 18 healthy young men (25.4 ±5.5 y, 81.2 ±11.6 kg). All muscle biopsies were obtained from the vastus lateralis muscle. Unilateral lower limb immobilization was preceded by four-weeks of exercise training to standardise acute training history, and 7 days of dietary provision to standardise energy/macronutrient intake. Dietary intake was also standardised/provided throughout the 14 d immobilization period.
2022-08-25 | PXD034908 | Pride
Project description:Ten-day human unilateral lower limb suspension and active recovery in young healthy men
| PRJNA869549 | ENA
Project description:To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice. Genes that showed increased expression with unloading and a Bcl-3 peak in the promoter (from ChIP-seq data) were considered as Bcl-3 direct targets during disuse atrophy. Using ChIP array, we identified 241 direct targets for Bcl-3. Our data describe Bcl-3 as a global regulator both of the proteolysis and the change in energy metabolism that are essential components of muscle atrophy due to disuse. Disuse skeletal muscle atrophy was induced by hind limb unloading. Weight bearing (WB) or 5-day hind limb unloaded (HU) muscles were harvested for total RNA isolation and processed for whole transcript expression profiling. We chose to examine gene expression and Bcl-3 binding from 5-day unloaded muscles because our previous time course study of disuse atrophy suggested that most genes are differentially regulated at this time point, and thus, would best represent the time for Bcl-3 binding to the gene targets of the NF-kB transcriptional network.
2012-11-10 | E-GEOD-40578 | biostudies-arrayexpress
Project description:Disuse muscle atrophy occurs consequent to prolonged limb immobility or bed rest, which represents an unmet medical need. As existing animal models of limb immobilization often cause skin erosion, edema, and other untoward effects, we here report an alternative method via thermoplastic immobilization of hindlimbs in mice. While significant decreases in the weight and fiber size were noted after 7 days of immobilization, no apparent skin erosion or edema was found. To shed light onto the molecular mechanism underlying this muscle wasting, we performed the next-generation sequencing analysis of gastrocnemius muscles from immobilized versus non-mobilized legs. Among a total of 55,487 genes analyzed, 787 genes were differentially expressed (> 4-fold; 454 and 333 genes up- and down-regulated, respectively), which included genes associated with muscle tissue development, muscle system process, protein digestion and absorption, and inflammation-related signaling. To the best our knowledge, this is the first study that used RNA-seq to reveal changes in the skeletal muscle transcriptome profiling in response to disuse atrophy without denervation. From a clinical perspective, this model may help understand the molecular/cellular mechanism that drives muscle disuse and identify therapeutic strategies for this debilitating disease.
2023-12-06 | GSE237537 | GEO
Project description:Extended periods of mechanical disuse can cause changes to the musculoskeletal system, particularly impacting the composition and strength of the affected muscle. Genetics are known to play a role in the proportion of lean mass and risk for sarcopenia with age, though the role of genetic variability in muscle adaptation to disuse is largely unknown. A total of 77 DO mice were casted using the single limb immobilization for three weeks, then hindlimb muscle morphology and performance were quantified. Total RNAseq was performed on gastrocnemius muscles, then Ingenuity Pathway Analysis was used to analyze sequencing data. We found that casting decreased body mass and hindlimb muscle mass (p<0.0001). Analyzing skeletal muscle morphology, we found an increase in cross-sectional area and volume in males but not females (p<0.0001). Additionally, we found immobilized limbs had greater twitch torque, but there was no effect on tetanus torque (p<0.0001). RNA sequencing identified 47 total significant differentially expressed genes. Finally, pathway analysis revealed a sex-dependent response to immobilization. Taken together, these results indicate that single limb immobilization incudes physiological changes to skeletal muscle and changes gene expression in a sex-dependent manner. Ultimately, this work will allow researchers to develop treatments to combat disuse-induced muscle loss.
2025-02-15 | GSE287100 | GEO
Project description:Advancements in animal models and cell culture techniques have been invaluable in the elucidation of molecular events and mechanisms regulating muscle atrophy. However, few studies have examined muscle atrophy in humans using modern experimental techniques. The purpose of this study was to examine and validate changes in global gene transcription during immobilization-induced muscle atrophy in humans. Healthy men and women (N=24) were subjected to two weeks of unilateral limb immobilization, with muscle biopsies obtained before, and after 48 hours (48H) and 14 days (14D) of immobilization. Both muscle cross sectional area (~ 5 %) and strength (10-20 %) were significantly reduced in men and women after 14D of immobilization. Micro-array analysis of total RNA extracted from biopsy samples uncovered 575 and 3,128 probes representing multiple genes, which were significantly altered at 48H and 14D, respectively. As a group, genes involved in mitochondrial bioenergetics and carbohydrate metabolism were predominant features at both 48H and 14D, with genes involved in protein synthesis and degradation significantly down-regulated and up-regulated, respectively, at 14D of muscle atrophy. There was also a significant decrease in the protein content of mitochondrial cytochrome c oxidase, and the enzyme activity of cytochrome c oxidase and citrate synthase after 14D of immobilization. Furthermore, protein ubiquitination and oxidative damage were significantly increased by 48H and 14D of immobilization, respectively. These results suggest that transcriptional and post-transcriptional suppression of mitochondrial processes is sustained throughout 14D of immobilization, while protein ubiquitination plays an early but transient role in the progression of immobilization-induced muscle atrophy in humans. 72 samples taken from quadriceps of healthy ambulatory young men and women. Samples were taken at 3 timepoints throughout a 14 day period, the initial sample was taken at time 0 (PRECAST), then the limb was immobilized via a brace, and the 2nd sample was taken at 48 hours (CAST02D). The third sample was taken following 14 days of immobilization (CAST14D).
2009-02-21 | E-GEOD-14901 | biostudies-arrayexpress
Project description:To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice. Genes that showed increased expression with unloading and a Bcl-3 peak in the promoter (from ChIP-seq data) were considered as Bcl-3 direct targets during disuse atrophy. Using ChIP array, we identified 241 direct targets for Bcl-3. Our data describe Bcl-3 as a global regulator both of the proteolysis and the change in energy metabolism that are essential components of muscle atrophy due to disuse.
2012-11-10 | GSE40578 | GEO
Project description:To evaluate decellularized skeletal muscle extracellular matrix hydrogel effectiveness in treating disuse atrophy using a mouse hindlimb suspension (HU) model. Male C57BL/6J mice were subjected to 5 days of hind limb unloading then received intramuscular matrix gel on the left TA. We then performed gene expression profiling analysis using data obtained from RNA-seq from mouse TA muscles (n=4 for matrix gel treatment, n=4 for PBS control , and n=4 for uninjured control) at day 7 post matrix gel injection
2023-01-02 | GSE220641 | GEO
Project description:Effects of 48h Lower Limb Unloading in Human Skeletal Muscle
| PRJNA126009 | ENA
Project description:Advancements in animal models and cell culture techniques have been invaluable in the elucidation of molecular events and mechanisms regulating muscle atrophy. However, few studies have examined muscle atrophy in humans using modern experimental techniques. The purpose of this study was to examine and validate changes in global gene transcription during immobilization-induced muscle atrophy in humans. Healthy men and women (N=24) were subjected to two weeks of unilateral limb immobilization, with muscle biopsies obtained before, and after 48 hours (48H) and 14 days (14D) of immobilization. Both muscle cross sectional area (~ 5 %) and strength (10-20 %) were significantly reduced in men and women after 14D of immobilization. Micro-array analysis of total RNA extracted from biopsy samples uncovered 575 and 3,128 probes representing multiple genes, which were significantly altered at 48H and 14D, respectively. As a group, genes involved in mitochondrial bioenergetics and carbohydrate metabolism were predominant features at both 48H and 14D, with genes involved in protein synthesis and degradation significantly down-regulated and up-regulated, respectively, at 14D of muscle atrophy. There was also a significant decrease in the protein content of mitochondrial cytochrome c oxidase, and the enzyme activity of cytochrome c oxidase and citrate synthase after 14D of immobilization. Furthermore, protein ubiquitination and oxidative damage were significantly increased by 48H and 14D of immobilization, respectively. These results suggest that transcriptional and post-transcriptional suppression of mitochondrial processes is sustained throughout 14D of immobilization, while protein ubiquitination plays an early but transient role in the progression of immobilization-induced muscle atrophy in humans.
2009-02-21 | GSE14901 | GEO