Normal mammalian skeletal muscle and its phenotypic plasticity

SUMMARYSince muscle mass makes up such a high proportion of total body mass, there must have been considerable selective pressure to minimize the cost of maintenance and to maximize the functionality of muscle tissue for all species. Phenotypic plasticity of muscle tissue allows the species blueprint of muscle tissue to be modified to accommodate specific demands experienced by animals over their lifetime. In this review, we report the scaling of muscle structural compartments in a set of mammals spanning five orders of magnitude(17 g woodmice to 450 kg horses and steers). Muscle mass, muscle myofibrillar volume and sarcoplasmic space were found to represent similar relative quantities in all species studies (scaling factor close to unity). Mitochondrial volumes were found to be systematically smaller in larger animals (scaling factor 0.91) and closely related to the scaling of V̇O2max (0.92) and were tracked by the scaling of total capillary length (0.95). In this set of species, we therefore found that maximal metabolic rate and supporting structures did not scale to the 0.75 power of body mass as generally suggested. Muscle phenotypic plasticity is reasonably well characterized on a structural and functional basis, but we still know little about the signals that cause the changes in gene expression necessary for phenotypic changes in muscle. The molecular responses of human m. vastus lateralis to endurance exercise indicate that a single bout of exercise causes specific transient transcriptional adaptations that may gradually accumulate after their translation into the (structural) modifications seen with phenotypic plasticity. Metabolic and mechanical factors are recognized candidate factors for the control of exercise-induced gene transcription in muscle. Distinct protein kinases and transcription factors emerge as possible interfaces that integrate the mechanical (MAPKs and jun/fos) and metabolic (AMPK, HIF-1αand PPARα) stimuli into enhanced gene transcription in skeletal muscle.

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Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00883.2012 ◽

2013 ◽

Vol 114 (11) ◽

pp. 1527-1535 ◽

Cited By ~ 31

Author(s):

Desy Salvadego ◽

Rossana Domenis ◽

Stefano Lazzer ◽

Simone Porcelli ◽

Jörn Rittweger ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Training ◽

Muscle Mass ◽

Body Mass ◽

Mitochondrial Respiration ◽

Ex Vivo ◽

Vastus Lateralis ◽

Whole Body ◽

Vastus Lateralis Muscle ◽

Oxidative Function

Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA; body mass 102.6 ± 7.3 kg, mean ± SD) and 11 controls (CTRL; body mass 77.8 ± 6.0 kg). Pulmonary O2 uptake (V̇o2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross-sectional area, volume (determined by magnetic resonance imaging), and strength were greater in RTA vs. CTRL (by ∼40%, ∼33%, and ∼20%, respectively). V̇o2peak during CE was higher in RTA vs. CTRL (4.05 ± 0.64 vs. 3.56 ± 0.30 l/min); no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE), V̇o2 peak was lower (by 15–20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, during both CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.7 ± 23.7 pmol O2·s−1·mg−1 ww) vs. CTRL (35.7 ± 10.2 pmol O2·s−1·mg−1 ww) and a tighter coupling of oxidative phosphorylation. In RTA, the greater muscle mass and maximal force and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise and unchanged efficiency and O2 cost at submaximal exercise, despite a much greater body mass.

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Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

Scientific Reports ◽

10.1038/s41598-021-81037-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anandini Swaminathan ◽

Andrej Fokin ◽

Tomas Venckūnas ◽

Hans Degens

Keyword(s):

Skeletal Muscle ◽

Glucose Tolerance ◽

Muscle Mass ◽

Body Mass ◽

High Fat Diet ◽

Control Diet ◽

Metabolic Health ◽

High Fat ◽

Methionine Restriction ◽

Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

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No Change of Body Mass, Fat Mass, and Skeletal Muscle Mass in Ultraendurance Swimmers After 12 Hours of Swimming

Research Quarterly for Exercise and Sport ◽

10.1080/02701367.2009.10599530 ◽

2009 ◽

Vol 80 (1) ◽

pp. 62-70 ◽

Cited By ~ 10

Author(s):

Beat Knechtle ◽

Patrizia Knechtle ◽

René Kaul ◽

Götz Kohler

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Body Mass ◽

Fat Mass ◽

Skeletal Muscle Mass

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Impaired expression and insulin-stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00485.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. E8-E15 ◽

Cited By ~ 27

Author(s):

Aidar R. Gosmanov ◽

Guillermo E. Umpierrez ◽

Ana H. Karabell ◽

Ruben Cuervo ◽

Donald B. Thomason

Keyword(s):

Skeletal Muscle ◽

Protein Expression ◽

Insulin Therapy ◽

Vastus Lateralis ◽

Vastus Lateralis Muscle ◽

Mammalian Skeletal Muscle ◽

Obese Patients ◽

Physiological Concentration ◽

Atypical Diabetes ◽

Muscle Biopsies

Although a pharmacological dose of insulin produces a dramatic increase in phosphorylation and activity of Akt isoforms 1 and 2 in mammalian skeletal muscle, few studies have examined the effect of physiological concentrations of insulin on the phosphorylation of Akt-1 and -2 in normal and diabetic tissue. This study examined the patterns of insulin-stimulated Akt isoform phosphorylation and protein expression in muscle biopsies obtained from obese patients with atypical diabetes immediately after a hyperglycemic crisis and again after near-normoglycemic remission. In obese patients with new-onset diabetes mellitus presenting with hyperglycemic crisis (plasma glucose 30.5 ± 4.8 mM), in vitro stimulation of vastus lateralis muscle biopsies with 100 μU/ml (0.6 nM) insulin increased insulin receptor phosphorylation threefold and Akt-1 phosphorylation on Ser473 twofold, whereas Akt-2 phosphorylation was not stimulated. After 10-wk intensive insulin therapy that led to near-normoglycemic remission and discontinuation of insulin therapy, both Akt-2 expression and insulin-stimulated Akt-2 Ser474 phosphorylation doubled. Hyperglycemic crisis did not affect insulin-stimulated threonine phosphorylation of either Akt-1 or Akt-2. The decreased Akt-2 expression at presentation was accompanied by reduced GLUT4 protein expression and increased expression of enzymes counterregulatory to insulin action. Thus a physiological concentration of insulin stimulated Akt-1 and Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression and stimulation appeared to be impaired in muscle of obese patients with atypical diabetes presenting with severe hyperglycemia.

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Comparison of methods to identify individuals with obesity at increased risk of functional impairment among a population of home-dwelling older adults

British Journal Of Nutrition ◽

10.1017/s0007114521004128 ◽

2021 ◽

pp. 1-8

Author(s):

Anne Lene Nordengen ◽

Linn Kristin Lie Øyri ◽

Stine Marie Ulven ◽

Truls Raastad ◽

Kirsten Bjørklund Holven ◽

...

Keyword(s):

Older Adults ◽

Muscle Strength ◽

Muscle Mass ◽

Body Mass ◽

Functional Impairment ◽

Muscle Quality ◽

Obese Women ◽

Total Body Mass ◽

Increased Risk ◽

Total Body

Abstract Obesity is associated with increased muscle mass and muscle strength. Methods taking into account the total body mass to reveal obese older individuals at increased risk of functional impairment are needed. Therefore, we aimed to detect methods to identify obese older adults at increased risk of functional impairment. Home-dwelling older adults (n 417, ≥ 70 years of age) were included in this cross-sectional study. Sex-specific cut-off points for two obesity phenotypes (waist circumference (WC) and body fat mass (FM %)) were used to divide women and men into obese and non-obese groups, and within-sex comparisons were performed. Obese women and men, classified by both phenotypes, had similar absolute handgrip strength (HGS) but lower relative HGS (HGS/total body mass) (P < 0·001) than non-obese women and men, respectively. Women with increased WC and FM %, and men with increased WC had higher appendicular skeletal muscle mass (P < 0·001), lower muscle quality (HGS/upper appendicular muscle mass) (P < 0·001), and spent longer time on the stair climb test and the repeated sit-to-stand test (P < 0·05) than non-obese women and men, respectively. Absolute muscle strength was not able to discriminate between obese and non-obese older adults. However, relative muscle strength in particular, but also muscle quality and physical performance tests, where the total body mass was taken into account or served as an extra load, identified obese older adults at increased risk of functional impairment. Prospective studies are needed to determine clinically relevant cut-off points for relative HGS in particular.

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Overfeeding and Substrate Availability, But Not Age or BMI, Alter Human Satellite Cell Function

Nutrients ◽

10.3390/nu12082215 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2215

Author(s):

Dane W. Fausnacht ◽

Ryan P. McMillan ◽

Nabil E. Boutagy ◽

Ryan A. Lupi ◽

Mordecai M. Harvey ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Mass Index ◽

Body Mass ◽

Cellular Proliferation ◽

Cell Function ◽

Vastus Lateralis ◽

Acid Oxidation ◽

Growth Media ◽

Percentage Difference

Satellite cells (SC) aid skeletal muscle growth and regeneration. SC-mediated skeletal muscle repair can both be influenced by and exacerbate several diseases linked to a fatty diet, obesity, and aging. The purpose of this study was to evaluate the effects of different lifestyle factors on SC function, including body mass index (BMI), age, and high-fat overfeeding. For this study, SCs were isolated from the vastus lateralis of sedentary young (18–30 years) and sedentary older (60–80 years) men with varying BMIs (18–32 kg/m2), as well as young sedentary men before and after four weeks of overfeeding (OVF) (55% fat/ + 1000 kcal, n = 4). The isolated SCs were then treated in vitro with a control (5 mM glucose, 10% fetal bovine serum (FBS)) or a high substrate growth media (HSM) (10% FBS, 25 mM glucose, and 400 μM 2:1 oleate–palmitate). Cells were assessed on their ability to proliferate, differentiate, and fuel substrate oxidation after differentiation. The effect of HSM was measured as the percentage difference between SCs exposed to HSM compared to control media. In vitro SC function was not affected by donor age. OVF reduced SC proliferation rates (–19% p < 0.05) but did not influence differentiation. Cellular proliferation in response to HSM was correlated to the donor’s body mass index (BMI) (r2 = 0.6121, p < 0.01). When exposed to HSM, SCs from normal weight (BMI 18–25 kg/m2) participants exhibited reduced proliferation and fusion rates with increased fatty-acid oxidation (p < 0.05), while SCs from participants with higher BMIs (BMI 25–32 kg/m2) demonstrated enhanced proliferation in HSM. HSM reduced proliferation and fusion (p < 0.05) in SCs isolated from subjects before OVF, whereas HSM exposure accelerated proliferation and fusion in SCs collected following OVF. These results indicated that diet has a greater influence on SC function than age and BMI. Though age and BMI do not influence in vitro SC function when grown in controlled conditions, both factors influenced the response of SCs to substrate challenges, indicating age and BMI may mediate responses to diet.

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Total Body Mass, Fat Mass, Fat-Free Mass, and Skeletal Muscle in Older People: Cross-Sectional Differences in 60-Year-Old Persons

Journal of the American Geriatrics Society ◽

10.1111/j.1532-5415.2001.49272.x ◽

2001 ◽

Vol 49 (12) ◽

pp. 1633-1640 ◽

Cited By ~ 120

Author(s):

Ursula G. Kyle ◽

Laurence Genton ◽

Didier Hans ◽

Veronique L. Karsegard ◽

Jean-Pierre Michel ◽

...

Keyword(s):

Skeletal Muscle ◽

Older People ◽

Body Mass ◽

Fat Mass ◽

Fat Free Mass ◽

Cross Sectional ◽

Total Body Mass ◽

Total Body

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Low skeletal muscle mass is associated with the risk of all-cause mortality in patients with type 2 diabetes mellitus

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018819842971 ◽

2019 ◽

Vol 10 ◽

pp. 204201881984297

Author(s):

Hitomi Miyake ◽

Ippei Kanazawa ◽

Ken-ichiro Tanaka ◽

Toshitsugu Sugimoto

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Type 2 Diabetes Mellitus ◽

Muscle Mass ◽

Body Mass ◽

Skeletal Muscle Mass ◽

Historical Cohort ◽

All Cause Mortality

Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of muscle mass reduction. However, the association between muscle mass and mortality in T2DM remains unknown. Methods: This was a historical cohort study with the endpoint of all-cause mortality. This study included 163 Japanese men and 141 postmenopausal women with T2DM whose body compositions were evaluated using dual-energy X-ray absorptiometry. Low muscle mass was defined as a skeletal muscle mass index (SMI) of <7.0 kg/m2 for men and <5.4 kg/m2 for women. Results: During the 6-year follow-up period, 32 men and 14 women died. In a Cox regression analysis adjusted for age, T2DM duration, glycated hemoglobin, serum creatinine, fasting C-peptide, body mass index, and lean body mass were associated with the risk of mortality in men [hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 1.00–3.28 per standard deviation (SD) decrease, p = 0.049] and women (HR = 4.53, 95% CI = 1.14–17.96 per SD decrease, p = 0.032). Neither fat mass nor bone mineral content was associated with mortality. Low SMI was associated with increased mortality in women (HR = 5.97, 95% CI = 1.04–34.37, p = 0.045), while the association between low SMI and mortality was marginal in men (HR = 2.38, 95% CI = 0.92–6.14, p = 0.074). Conclusions: Low muscle mass was independently associated with all-cause mortality in patients with T2DM. The preservation of skeletal muscle mass is important to protect patients with T2DM from increased mortality risk.

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Prognostic value of low skeletal muscle mass in patient treated by exclusive curative radiochemotherapy for a NSCLC

Scientific Reports ◽

10.1038/s41598-021-90187-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

R. Mallet ◽

P. Decazes ◽

R. Modzelewski ◽

J. Lequesne ◽

P. Vera ◽

...

Keyword(s):

Skeletal Muscle ◽

Overall Survival ◽

Prognostic Factor ◽

Muscle Mass ◽

Body Mass ◽

Visceral Fat ◽

Prognostic Value ◽

Skeletal Muscle Mass ◽

Pet Ct ◽

Cox Analysis

AbstractLow skeletal muscle mass is a well-known prognostic factor for patients treated for a non-small-cell lung cancer by surgery or chemotherapy. However, its impact in patients treated by exclusive radiochemotherapy has never been explored. Our study tries to evaluate the prognostic value of low skeletal muscle mass and other antropometric parameters on this population. Clinical, nutritional and anthropometric date were collected for 93 patients treated by radiochemotherapy for a NSCLC. Anthropometric parameters were measured on the PET/CT by two methods. The first method was a manual segmentation at level L3, used to define Muscle Body Area (MBAL3), Visceral Fat Area (VFAL3) and Subcutaneous Fat Area (SCFAL3). The second method was an software (Anthropometer3D), allowing an automatic multislice measurement of Lean Body Mass (LBMAnthro3D), Fat Body Mass (FBMAnthro3D), Muscle Body Mass (MBMAnthro3D), Visceral Fat Mass (VFMAnthro3D), and Sub-Cutaneous Fat Mass (SCFMAnthro3D) on the PET/CT. All anthropometrics parameters were normalised by the patient's height. The primary end point was overall survival time. Univariate and then stepwise multivariate cox analysis were performed for significant parameters. Finally, Spearman's correlation between MBAL3 and MBMAnthro3D was assessed. Forty-one (44%) patients had low skeletal muscle mass. The median overall survival was 18 months for low skeletal muscle mass patients versus 36 months for non-low skeletal muscle mass patients (p = 0.019). Low skeletal muscle mass (HR = 1.806, IC95% [1.09–2.98]), serums albumin level < 35 g/l (HR = 2.203 [1.19–4.09]), Buzby Index < 97.5 (HR = 2.31 [1.23–4.33]), WHO score = 0 (HR = 0.59 [0.31–0.86] and MBMAnthro3D < 8.56 kg/m2 (HR = 2.36 [1.41–3.90]) were the only significant features in univariates analysis. In the stepwise multivariate Cox analysis, only MBMAnthro3D < 8.56 kg/m2 (HR = 2.16, p = 0.003) and WHO score = 0 (HR = 0.59, p = 0.04) were significant. Finally, muscle quantified by MBAL3 and MBMAnthro3D were found to be highly correlated (Spearman = 0.9). Low skeletal muscle mass, assessed on the pre-treatment PET/CT is a powerful prognostic factor in patient treated by radiochemotherapy for a NSCLC. The automatic software Anthropometer3D can easily identify patients a risk that could benefit an adapted therapy.

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