Exposure to High Altitude Promotes Loss of Muscle Mass That Is Not Rescued by Metformin

Fullerton, Zackery S.; McNair, Benjamin D.; Marcello, Nicholas A.; Schmitt, Emily E.; Bruns, Danielle R.

doi:10.1089/ham.2022.0015

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…In this study, we found a negative correlation between 9 body compositions (BFT, LBM, TBW, MM, SBW, BMR, TEE, TP, and Is) and HA, and 7 indicators (LBM, TBW, MM, SBW, BMR, TP, and Is) showed significant differences in different altitude stratification in the Tibetan college students. Similarly, these indicators have previously been reported to decrease with increasing altitude (7,8,20). In addition, inverse association between obesity and altitude has previously been reported (21).…”

Section: Discussionmentioning

confidence: 62%

“…Sympathetic activity is reduced during prolonged exposure to HA, resulting in a decrease in basal metabolic rate (BMR) ( 6 ). Additionally, exposure to HA hypoxic environment can lead to serious loss of muscle mass (MM), which results in skeletal muscle atrophy ( 8 ). Participants living at sea level tend to be taller, heavier, and have a higher body mass index (BMI), and waist circumference (WC) relative to those living at HA ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Novel insight into the genetic signatures of altitude adaptation related body composition in Tibetans

Li,

Xu,

et al. 2024

Front. Public Health

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BackgroundThe Tibetan population residing in high-altitude (HA) regions has adapted to extreme hypoxic environments. However, there is limited understanding of the genetic basis of body compositions in Tibetan population adapted to HA.MethodsWe performed a genome-wide association study (GWAS) to identify genetic variants associated with HA and HA-related body composition traits. A total of 755,731 single nucleotide polymorphisms (SNPs) were genotyped using the precision medicine diversity array from 996 Tibetan college students. T-tests and Pearson correlation analysis were used to estimate the association between body compositions and altitude. The mixed linear regression identified the SNPs significantly associated with HA and HA-related body compositions. LASSO regression was used to screen for important SNPs in HA and body compositions.ResultsSignificant differences were observed in lean body mass (LBW), muscle mass (MM), total body water (TBW), standard weight (SBW), basal metabolic rate (BMR), total protein (TP), and total inorganic salt (Is) in different altitudes stratification. We identified three SNPs in EPAS1 (rs1562453, rs7589621 and rs7583392) that were significantly associated with HA (p < 5 × 10−7). GWAS analysis of 7 HA-related body composition traits, we identified 14 SNPs for LBM, 11 SNPs for TBW, 15 SNPs for MM, 16 SNPs for SBW, 9 SNPs for BMR, 12 SNPs for TP, and 26 SNPs for Is (p < 5.0 × 10−5).ConclusionThese findings provide insight into the genetic basis of body composition in Tibetan college students adapted to HA, and lay the foundation for further investigation into the molecular mechanisms underlying HA adaptation.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Novel insight into the genetic signatures of altitude adaptation related body composition in Tibetans

Li,

Xu,

et al. 2024

Front. Public Health

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“…During the period of acclimatization when populations residing in lowland areas transition to high-altitude regions, the distinctive environmental stimuli of the elevated terrain may result in a certain degree of skeletal muscle atrophy 1 , potentially leading to adverse effects on muscle functionality. Hypoxia is acknowledged as one of the contributing factors to skeletal muscle atrophy in high-altitude environments, alongside factors such as reduced atmospheric pressure and dietary shifts.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia treatment and resistance training alters microRNA profiling in rats skeletal muscle

Mei,

Hu,

Zhang

et al. 2024

Sci Rep

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MicroRNAs (miRNAs) may play a crucial regulatory role in the process of muscle atrophy induced by high-altitude hypoxia and its amelioration through resistance training. However, research in this aspect is still lacking. Therefore, this study aimed to employ miRNA microarray analysis to investigate the expression profile of miRNAs in skeletal muscle from an animal model of hypoxia-induced muscle atrophy and resistance training aimed at mitigating muscle atrophy. The study utilized a simulated hypoxic environment (oxygen concentration at 11.2%) to induce muscle atrophy and established a rat model of resistance training using ladder climbing, with a total intervention period of 4 weeks. The miRNA expression profile revealed 9 differentially expressed miRNAs influenced by hypoxia (e.g., miR-341, miR-32-5p, miR-465-5p) and 14 differentially expressed miRNAs influenced by resistance training under hypoxic conditions (e.g., miR-338-5p, miR-203a-3p, miR-92b-3p) (∣log2(FC)∣ ≥ 1.5, p < 0.05). The differentially expressed miRNAs were found to target genes involved in muscle protein synthesis and degradation (such as Utrn, mdm2, eIF4E), biological processes (such as negative regulation of transcription from RNA polymerase II promoter, regulation of transcription, DNA-dependent), and signaling pathways (such as Wnt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, mTOR signaling pathway). This study provides a foundation for understanding and further exploring the molecular mechanisms underlying hypoxia-induced rats muscle atrophy and the mitigation of atrophy through resistance training.

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Hypoxia-Induced Skeletal Muscle Atrophy and Evaluating the Efficacy of Resistance Training: Insights from microRNA Expression Profiling and Bioinformatics Analysis

Mei,

Hu,

Zhang

et al. 2023

Preprint

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MicroRNAs (miRNAs) may play a crucial regulatory role in the process of muscle atrophy induced by high-altitude hypoxia and its amelioration through resistance training. However, research in this aspect is still lacking. Therefore, this study aimed to employ miRNA microarray analysis to investigate the expression profile of miRNAs in skeletal muscle from an animal model of hypoxia-induced muscle atrophy and resistance training aimed at mitigating muscle atrophy. The study utilized a simulated hypoxic environment (oxygen concentration at 11.2%) to induce muscle atrophy and established a rat model of resistance training using ladder climbing, with a total intervention period of 4 weeks. The miRNA expression profile revealed 9 differentially expressed miRNAs influenced by hypoxia (e.g., miR-341, miR-32-5p, miR-465-5p) and 14 differentially expressed miRNAs influenced by resistance training under hypoxic conditions (e.g., miR-338-5p, miR-203a-3p, miR-92b-3p) (∣Fold Change∣≥1.5, p༜0.05). The differentially expressed miRNAs were found to target genes involved in muscle protein synthesis and degradation (such as Utrn, mdm2, eIF4E), biological processes (such as negative regulation of transcription from RNA polymerase II promoter, regulation of transcription, DNA-dependent), and signaling pathways (such as Wnt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, mTOR signaling pathway). This study provides a foundation for understanding and further exploring the molecular mechanisms underlying hypoxia-induced muscle atrophy and the mitigation of atrophy through resistance training.

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Exposure to High Altitude Promotes Loss of Muscle Mass That Is Not Rescued by Metformin

Cited by 3 publications

References 41 publications

Novel insight into the genetic signatures of altitude adaptation related body composition in Tibetans

Novel insight into the genetic signatures of altitude adaptation related body composition in Tibetans

Hypoxia treatment and resistance training alters microRNA profiling in rats skeletal muscle

Hypoxia-Induced Skeletal Muscle Atrophy and Evaluating the Efficacy of Resistance Training: Insights from microRNA Expression Profiling and Bioinformatics Analysis

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