Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy

Regulators of skeletal muscle mass are of interest, given the morbidity and mortality of muscle atrophy and myopathy. Four-and-a-half LIM protein 1 (FHL1) is mutated in several human myopathies, including reducing-body myopathy (RBM). The normal function of FHL1 in muscle and how it causes myopathy remains unknown. We find that FHL1 transgenic expression in mouse skeletal muscle promotes hypertrophy and an oxidative fiber-type switch, leading to increased whole-body strength and fatigue resistance. Additionally, FHL1 overexpression enhances myoblast fusion, resulting in hypertrophic myotubes in C2C12 cells, (a phenotype rescued by calcineurin inhibition). In FHL1-RBM C2C12 cells, there are no hypertrophic myotubes. FHL1 binds with the calcineurin-regulated transcription factor NFATc1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1), enhancing NFATc1 transcriptional activity. Mutant RBM-FHL1 forms aggregate bodies in C2C12 cells, sequestering NFATc1 and resulting in reduced NFAT nuclear translocation and transcriptional activity. NFATc1 also colocalizes with mutant FHL1 to reducing bodies in RBM-afflicted skeletal muscle. Therefore, via NFATc1 signaling regulation, FHL1 appears to modulate muscle mass and strength enhancement.

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Association between hand muscle thickness and whole-body skeletal muscle mass in healthy adults: a pilot study

Journal of Physical Therapy Science ◽

10.1589/jpts.29.1644 ◽

2017 ◽

Vol 29 (9) ◽

pp. 1644-1648 ◽

Cited By ~ 6

Author(s):

Akio Morimoto ◽

Tadashi Suga ◽

Nobuaki Tottori ◽

Michio Wachi ◽

Jun Misaki ◽

...

Keyword(s):

Skeletal Muscle ◽

Pilot Study ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Thickness ◽

Healthy Adults ◽

Whole Body ◽

Hand Muscle

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Alternate Mediterranean diet score is positively associated with skeletal muscle mass index in middle-aged adults

British Journal Of Nutrition ◽

10.1017/s0007114517001118 ◽

2017 ◽

Vol 117 (8) ◽

pp. 1181-1188 ◽

Cited By ~ 9

Author(s):

Hui-yuan Tian ◽

Rui Qiu ◽

Li-peng Jing ◽

Zhan-yong Chen ◽

Geng-dong Chen ◽

...

Keyword(s):

Skeletal Muscle ◽

Mediterranean Diet ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

General Information ◽

Whole Body ◽

Cross Sectional ◽

Mediterranean Diet Score ◽

Skeletal Muscle Mass Index ◽

Diet Score

AbstractResearches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40–75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008–2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011–2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all Ptrend<0·05). The multiple covariate-adjusted SMI means were 2·70 % (whole body), 2·65 % (limbs), 2·50 % (arms) and 2·70 % (legs) higher in the high (v. low) category aMDS in males (all P<0·05). In females, the corresponding values were 1·35 % (Ptrend=0·03), 1·05, 0·52 and 1·20 %, (Ptrend>0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (Pinteraction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.

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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.

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Japanese radio calisthenics prevents the reduction of skeletal muscle mass volume in people with type 2 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001027 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001027 ◽

Cited By ~ 1

Author(s):

Tomonori Kimura ◽

Takuro Okamura ◽

Keiko Iwai ◽

Yoshitaka Hashimoto ◽

Takafumi Senmaru ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Resistance Training ◽

Muscle Mass ◽

High Intensity ◽

Skeletal Muscle Mass ◽

Whole Body ◽

Therapeutic Exercises ◽

The Difference

ObjectiveReduction of muscle mass and strength is an important treatment target for patients with type 2 diabetes. Recent studies have reported that high-intensity resistance training improves physical function; however, all patients found it difficult to perform high-intensity resistance training. Radio calisthenics, considered as therapeutic exercises to promote health in Japan, are simple exercises that can be performed regardless of age and help move the muscles and joints of the whole body effectively according to the rhythm of radio. We investigated the efficacy of radio calisthenics for muscle mass in patients with type 2 diabetes in this retrospective cohort study.Research design and methodsA total of 42 hospitalized patients with type 2 diabetes were recruited. The skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg) divided by height squared (m2). We defined the change of SMI as the difference of SMI between the beginning and end of hospitalization.ResultsAmong 42 patients, 15 (11 men and 4 women) performed radio calisthenics. Body weights of both radio calisthenics exercisers and non-exercisers decreased during hospitalization. The change of SMI was significantly lesser in radio calisthenics exercisers than in non-exercisers (7.1±1.4 to 7.1±1.3, –0.01±0.09 vs 6.8±1.1 to 6.5±1.2, –0.27±0.06 kg/m2, p=0.016). The proportion of decreased SMI was 85.2% (23/27 patients) in non-radio calisthenics exercisers, whereas that in radio calisthenics exercisers was 46.7% (7/15 patients).ConclusionsRadio calisthenics prevent the reduction of skeletal muscle mass. Thus, radio calisthenics can be considered effective for patients with type 2 diabetes.

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Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.01322.2006 ◽

2007 ◽

Vol 102 (6) ◽

pp. 2142-2148 ◽

Cited By ~ 30

Author(s):

Sean Walsh ◽

E. Jeffrey Metter ◽

Luigi Ferrucci ◽

Stephen M. Roth

Keyword(s):

Skeletal Muscle ◽

Genetic Variation ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Fat Free Mass ◽

Negative Regulator ◽

Interindividual Variation ◽

Whole Body ◽

Haplotype Structure ◽

Type Ii

Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double-muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B ( ACVR2B) are two myostatin-related genes involved in the regulation and signaling of myostatin. We sought to identify associations between genetic variation and haplotype structure in both follistatin and ACVR2B with skeletal muscle-related phenotypes. Three hundred fifteen men and 278 women aged 19–90 yr from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings (Hap Groups) based on HapMap data. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. Women carriers of ACVR2B Hap Group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for Hap Group 2 (109.2 ± 1.9 vs. 118.6 ± 4.1 N·m, 30°/s, respectively, P = 0.036). No significant association was observed in men. Male carriers of follistatin Hap Group 3 exhibited significantly less total leg fat-free mass than noncarriers (16.6 ± 0.3 vs. 17.5 ± 0.2 kg, respectively, P = 0.012). No significant associations between these haplotype groups were observed in women. These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships.

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Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women

Applied Physiology Nutrition and Metabolism ◽

10.1139/h08-060 ◽

2008 ◽

Vol 33 (4) ◽

pp. 769-774 ◽

Cited By ~ 32

Author(s):

Jennifer L. Kuk ◽

Katherine Kilpatrick ◽

Lance E. Davidson ◽

Robert Hudson ◽

Robert Ross

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Muscle Mass ◽

Visceral Adipose Tissue ◽

Skeletal Muscle Mass ◽

Whole Body ◽

Men And Women ◽

Visceral Adipose

The relationship between skeletal muscle mass, visceral adipose tissue, insulin sensitivity, and glucose tolerance was examined in 214 overweight or obese, but otherwise healthy, men (n = 98) and women (n = 116) who participated in various exercise and (or) weight-loss intervention studies. Subjects had a 75 g oral glucose tolerance test and (or) insulin sensitivity measures by a 3 h hyperinsulinemic–euglycemic clamp technique. Whole-body skeletal muscle mass and visceral adipose tissue were measured using a multi-slice magnetic resonance imaging protocol. Total body skeletal muscle mass was not associated with any measure of glucose metabolism in men or women (p > 0.10). These observations remained independent of age and total adiposity. Conversely, visceral adipose tissue was a significant predictor of various measures of glucose metabolism in both men and women with or without control for age and (or) total body fat (p < 0.05). Although skeletal muscle is a primary site for glucose uptake and deposition, these findings suggest that unlike visceral adipose tissue, whole-body skeletal muscle mass per se is not associated with either glucose tolerance or insulin sensitivity in overweight and obese men and women.

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Sex differences in whole body skeletal muscle mass measured by magnetic resonance imaging and its distribution in young Japanese adults

British Journal of Sports Medicine ◽

10.1136/bjsm.37.5.436 ◽

2003 ◽

Vol 37 (5) ◽

pp. 436-440 ◽

Cited By ~ 129

Author(s):

T Abe

Keyword(s):

Magnetic Resonance Imaging ◽

Skeletal Muscle ◽

Sex Differences ◽

Magnetic Resonance ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Whole Body ◽

Resonance Imaging ◽

Japanese Adults

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Clinical Characteristics of Geriatric Patients With Non-Specific Chronic Low Back Pain

10.21203/rs.3.rs-812124/v1 ◽

2021 ◽

Author(s):

Yoshihito Sakai ◽

Norimitsu Wakao ◽

Hiroki Matsui ◽

Tsuyoshi Watanabe ◽

Hiroki Iida ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Geriatric Patients ◽

Whole Body ◽

Composition Analysis ◽

Sagittal Vertical Axis ◽

Distribution Width ◽

Age Related ◽

Lumbar Degeneration

Abstract Although the prevalence and the associated burden of LBP increase with age, research on LBP has primarily focused on young people and adults, and little attention has been given to the elderly population. Chronic inflammation is well-known as senescence associated secretory phenotype (SASP), which produces numerous proinflammatory cytokines leading to age-related inflammation. We enrolled 203 patients with an average age of 79.0 years, with non-specific CLBP; the patients were compared with age- and sex-matched controls without CLBP using a propensity score-matched analysis. We performed laboratory analysis, radiographic evaluations for global spinal parameter and lumbar degeneration assessment, and body composition analysis using whole-body dual-energy X-ray absorptiometry. We observed a higher red blood cell distribution width (RDW), as well as a lower skeletal muscle mass index and a higher fat mass in patients with CLBP. Moreover, patients with geriatric CLBP had significantly lower lumbar lordosis, and higher sagittal vertical axis was correlated with lower muscle mass in the extremities and trunk, independent of lumbar degeneration. Geriatric CLBP is associated with senescence. RDW, which is an index of aging, was high among elderly patients with CLBP. Furthermore, geriatric patients with CLBP often have age-related skeletal muscle mass reduction and spinal sagittal malalignment.

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Interrelationships among whole-body skeletal muscle mass, masseter muscle mass, oral function, and dentition status in older Japanese adults

BMC Geriatrics ◽

10.1186/s12877-021-02552-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Masanori Iwasaki ◽

Hirohiko Hirano ◽

Keiko Motokawa ◽

Maki Shirobe ◽

Ayako Edahiro ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Masseter Muscle ◽

Skeletal Muscle Mass ◽

Muscle Performance ◽

Whole Body ◽

Direct Path ◽

Occlusal Force ◽

Oral Function ◽

Japanese Adults

Abstract Background Generalized loss of skeletal muscle mass (SMM) may modulate or otherwise affect the loss of masseter muscle mass and be responsible for low masseter muscle performance and strength (i.e., low oral function). Moreover, dentition status can affect oral function independent of the muscle state. This cross-sectional study aimed to simultaneously investigate the relationships among whole-body SMM, masseter muscle mass, oral function (masseter muscle performance and strength), and dentition status in 1349 Japanese adults (mean age = 73.6 years). Methods We determined the estimated masseter muscle mass (e-MMM) based on morphological measurements of the masseter muscle. Masseter muscle performance was assessed via masticatory performance evaluation scores using gum, and strength was assessed as the maximal occlusal force. Dentition status was assessed as the number of functional teeth. SMM was measured by bioelectrical impedance analysis. Structural equation modeling stratified by sex was employed to investigate associations among SMM, e-MMM, gum score, occlusal force, and number of functional teeth. Results The direct path from SMM to e-MMM was statistically significant, as was the direct path from e-MMM to oral function (gum score and maximum occlusal force) for both sexes. We additionally confirmed that SMM indirectly affected gum score and maximum occlusal force via e-MMM (men; standardized coefficient [95% CI] = 3.64 [1.31 to 5.96] for maximum occlusal force and 0.01 [0.01 to 0.02] for gum score, women; 2.01 [0.38 to 3.81] for maximum occlusal force and 0.01 [0.002 to 0.01] for gum score). The number of functional teeth had direct effects on e-MMM, gum score, and maximum occlusal force. Conclusions Low SMM was significantly indirectly associated with poor oral function through a low masseter muscle mass, and dentition status was independently associated with oral function.

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