Changes in Muscle Mass and Composition by Exercise and Hypoxia as Assessed by DEXA in Mice

Background and Objective: Skeletal muscle is critical for overall health and predicts quality of life in several chronic diseases, thus quantification of muscle mass and composition is necessary to understand how interventions promote changes in muscle quality. The purpose of this investigation was to quantify changes in muscle mass and composition in two distinct pre-clinical models of changes in muscle quality using a clinical dual X-ray absorptiometry (DEXA), validated for use in mice. Materials and Methods: Adult C57Bl6 male mice were given running wheels (RUN; muscle hypertrophy) or placed in hypobaric hypoxia (HH; muscle atrophy) for four weeks. Animals received weekly DEXA and terminal collection of muscle hind limb complex (HLC) and quadriceps weights and signaling for molecular regulators of muscle mass and composition. Results: HH decreased total HLC muscle mass with no changes in muscle composition. RUN induced loss of fat mass in both the quadriceps and HLC. Molecular mediators of atrophy were upregulated in HH while stimulators of muscle growth were higher in RUN. These changes in muscle mass and composition were quantified by a clinical DEXA, which we described and validated for use in pre-clinical models. Conclusions: RUN improves muscle composition while HH promotes muscle atrophy, though changes in composition in hypoxia remain unclear. Use of the widely available clinical DEXA for use in mice enhances translational research capacity to understand the mechanisms by which atrophy and hypertrophy promote skeletal muscle and overall health.

Download Full-text

Skeletal muscle wasting in chronic kidney disease: the emerging role of microRNAs

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz193 ◽

2019 ◽

Vol 35 (9) ◽

pp. 1469-1478 ◽

Cited By ~ 5

Author(s):

Kate A Robinson ◽

Luke A Baker ◽

Matthew P M Graham-Brown ◽

Emma L Watson

Keyword(s):

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Muscle Mass ◽

Muscle Atrophy ◽

Muscle Wasting ◽

Muscle Growth ◽

Exciting Field ◽

Skeletal Muscle Wasting ◽

And Function

Abstract Skeletal muscle wasting is a common complication of chronic kidney disease (CKD), characterized by the loss of muscle mass, strength and function, which significantly increases the risk of morbidity and mortality in this population. Numerous complications associated with declining renal function and lifestyle activate catabolic pathways and impair muscle regeneration, resulting in substantial protein wasting. Evidence suggests that increasing skeletal muscle mass improves outcomes in CKD, making this a clinically important research focus. Despite extensive research, the pathogenesis of skeletal muscle wasting is not completely understood. It is widely recognized that microRNAs (miRNAs), a family of short non-coding RNAs, are pivotal in the regulation of skeletal muscle homoeostasis, with significant roles in regulating muscle growth, regeneration and metabolism. The abnormal expression of miRNAs in skeletal muscle during disease has been well described in cellular and animal models of muscle atrophy, and in recent years, the involvement of miRNAs in the regulation of muscle atrophy in CKD has been demonstrated. As this exciting field evolves, there is emerging evidence for the involvement of miRNAs in a beneficial crosstalk system between skeletal muscle and other organs that may potentially limit the progression of CKD. In this article, we describe the pathophysiological mechanisms of muscle wasting and explore the contribution of miRNAs to the development of muscle wasting in CKD. We also discuss advances in our understanding of miRNAs in muscle–organ crosstalk and summarize miRNA-based therapeutics currently in clinical trials.

Download Full-text

Relationships between insulin sensitivity, skeletal muscle mass and muscle quality in obese adolescent boys

European Journal of Clinical Nutrition ◽

10.1038/ejcn.2012.142 ◽

2012 ◽

Vol 66 (12) ◽

pp. 1366-1368 ◽

Cited By ~ 19

Author(s):

S Lee ◽

Y Kim ◽

D A White ◽

J L Kuk ◽

S Arslanian

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Quality ◽

Adolescent Boys ◽

Obese Adolescent

Download Full-text

Tail suspension is useful as a sarcopenia model in rats

Laboratory Animal Research ◽

10.1186/s42826-020-00083-9 ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Akira Nemoto ◽

Toru Goyagi

Keyword(s):

Skeletal Muscle ◽

Muscle Contraction ◽

Experimental Model ◽

Muscle Mass ◽

Muscle Atrophy ◽

Whole Body ◽

Skeletal Muscle Atrophy ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Simple Method

Abstract Background Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. Results Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. Conclusions TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

Download Full-text

Skeletal Muscle Atrophy and Hypertrophy

Pharmacotherapy of Cachexia ◽

10.1201/9781420048957.ch3 ◽

2005 ◽

pp. 31-48

Author(s):

David Glass

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy ◽

Atrophy And Hypertrophy

Download Full-text

Signaling Pathways that Regulate Skeletal Muscle Atrophy and Hypertrophy

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.407.2 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

David J. Glass

Keyword(s):

Skeletal Muscle ◽

Signaling Pathways ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy ◽

Atrophy And Hypertrophy

Download Full-text

Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways

Cellular and Molecular Life Sciences ◽

10.1007/s00018-014-1689-x ◽

2014 ◽

Vol 71 (22) ◽

pp. 4361-4371 ◽

Cited By ~ 152

Author(s):

J. Rodriguez ◽

B. Vernus ◽

I. Chelh ◽

I. Cassar-Malek ◽

J. C. Gabillard ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathways ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy ◽

Atrophy And Hypertrophy

Download Full-text

Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

International Journal of Molecular Sciences ◽

10.3390/ijms21051628 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1628 ◽

Cited By ~ 3

Author(s):

Keisuke Hitachi ◽

Masashi Nakatani ◽

Shiori Funasaki ◽

Ikumi Hijikata ◽

Mizuki Maekawa ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscle Mass ◽

Muscle Size ◽

Skeletal Muscle Atrophy ◽

Myostatin Gene ◽

Expression Levels ◽

Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

Download Full-text

Reference Values for Skeletal Muscle Mass – Current Concepts and Methodological Considerations

Nutrients ◽

10.3390/nu12030755 ◽

2020 ◽

Vol 12 (3) ◽

pp. 755 ◽

Cited By ~ 6

Author(s):

Carina O. Walowski ◽

Wiebke Braun ◽

Michael J. Maisch ◽

Björn Jensen ◽

Sven Peine ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Reference Values ◽

Skeletal Muscle Mass ◽

Bioelectrical Impedance ◽

Reference Population ◽

Muscle Quality ◽

Whole Body ◽

Whole Body Imaging ◽

Cross Sectional

Assessment of a low skeletal muscle mass (SM) is important for diagnosis of ageing and disease-associated sarcopenia and is hindered by heterogeneous methods and terminologies that lead to differences in diagnostic criteria among studies and even among consensus definitions. The aim of this review was to analyze and summarize previously published cut-offs for SM applied in clinical and research settings and to facilitate comparison of results between studies. Multiple published reference values for discrepant parameters of SM were identified from 64 studies and the underlying methodological assumptions and limitations are compared including different concepts for normalization of SM for body size and fat mass (FM). Single computed tomography or magnetic resonance imaging images and appendicular lean soft tissue by dual X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) are taken as a valid substitute of total SM because they show a high correlation with results from whole body imaging in cross-sectional and longitudinal analyses. However, the random error of these methods limits the applicability of these substitutes in the assessment of individual cases and together with the systematic error limits the accurate detection of changes in SM. Adverse effects of obesity on muscle quality and function may lead to an underestimation of sarcopenia in obesity and may justify normalization of SM for FM. In conclusion, results for SM can only be compared with reference values using the same method, BIA- or DXA-device and an appropriate reference population. Limitations of proxies for total SM as well as normalization of SM for FM are important content-related issues that need to be considered in longitudinal studies, populations with obesity or older subjects.

Download Full-text

Soluble Whey Protein Hydrolysate Ameliorates Muscle Atrophy Induced by Immobilization via Regulating the PI3K/Akt Pathway in C57BL/6 Mice

Nutrients ◽

10.3390/nu12113362 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3362

Author(s):

Ji Eun Shin ◽

Seok Jun Park ◽

Seung Il Ahn ◽

Se-Young Choung

Keyword(s):

Skeletal Muscle ◽

Whey Protein ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscle Mass ◽

Protein Hydrolysate ◽

Protein Hydrolysates ◽

Protein Supplementation ◽

Whey Protein Hydrolysates ◽

Whey Protein Hydrolysate

Sarcopenia, a loss of skeletal muscle mass and function, is prevalent in older people and associated with functional decline and mortality. Protein supplementation is necessary to maintain skeletal muscle mass and whey protein hydrolysates have the best nutrient quality among food proteins. In the first study, C57BL/6 mice were subjected to immobilization for 1 week to induce muscle atrophy. Then, mice were administered with four different whey protein hydrolysates for 2 weeks with continuous immobilization. Among them, soluble whey protein hydrolysate (WP-S) had the greatest increase in grip strength, muscle weight, and cross-sectional area of muscle fiber than other whey protein hydrolysates. To investigate the molecular mechanism, we conducted another experiment with the same experimental design. WP-S significantly promoted the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and inhibited the PI3K/Akt/forkhead box O (FoxO) pathway. In addition, it increased myosin heavy chain (MyHC) expression in both the soleus and quadriceps and changed MyHC isoform expressions. In conclusion, WP-S attenuated muscle atrophy induced by immobilization by enhancing the net protein content regulating muscle protein synthesis and degradation. Thus, it is a necessary and probable candidate for developing functional food to prevent sarcopenia.

Download Full-text