scholarly journals Signaling Pathways That Control Muscle Mass

2020 ◽  
Vol 21 (13) ◽  
pp. 4759 ◽  
Author(s):  
Anna Vainshtein ◽  
Marco Sandri

The loss of skeletal muscle mass under a wide range of acute and chronic maladies is associated with poor prognosis, reduced quality of life, and increased mortality. Decades of research indicate the importance of skeletal muscle for whole body metabolism, glucose homeostasis, as well as overall health and wellbeing. This tissue’s remarkable ability to rapidly and effectively adapt to changing environmental cues is a double-edged sword. Physiological adaptations that are beneficial throughout life become maladaptive during atrophic conditions. The atrophic program can be activated by mechanical, oxidative, and energetic distress, and is influenced by the availability of nutrients, growth factors, and cytokines. Largely governed by a transcription-dependent mechanism, this program impinges on multiple protein networks including various organelles as well as biosynthetic and quality control systems. Although modulating muscle function to prevent and treat disease is an enticing concept that has intrigued research teams for decades, a lack of thorough understanding of the molecular mechanisms and signaling pathways that control muscle mass, in addition to poor transferability of findings from rodents to humans, has obstructed efforts to develop effective treatments. Here, we review the progress made in unraveling the molecular mechanisms responsible for the regulation of muscle mass, as this continues to be an intensive area of research.

1997 ◽  
Vol 83 (1) ◽  
pp. 229-239 ◽  
Author(s):  
Dympna Gallagher ◽  
Marjolein Visser ◽  
Ronald E. De Meersman ◽  
Dennis Sepúlveda ◽  
Richard N. Baumgartner ◽  
...  

Gallagher, Dympna, Marjolein Visser, Ronald E. De Meersman, Dennis Sepúlveda, Richard N. Baumgartner, Richard N. Pierson, Tamara Harris, and Steven B. Heymsfield. Appendicular skeletal muscle mass: effects of age, gender, and ethnicity. J. Appl. Physiol. 83(1): 229–239, 1997.—This study tested the hypothesis that skeletal muscle mass is reduced in elderly women and men after adjustment first for stature and body weight. The hypothesis was evaluated by estimating appendicular skeletal muscle mass with dual-energy X-ray absorptiometry in a healthy adult cohort. A second purpose was to test the hypothesis that whole body40K counting-derived total body potassium (TBK) is a reliable indirect measure of skeletal muscle mass. The independent effects on both appendicular skeletal muscle and TBK of gender ( n = 148 women and 136 men) and ethnicity ( n = 152 African-Americans and 132 Caucasians) were also explored. Main findings were 1) for both appendicular skeletal muscle mass (total, leg, and arm) and TBK, age was an independent determinant after adjustment first by stepwise multiple regression for stature and weight (multiple regression model r 2 = ∼0.60); absolute decrease with greater age in men was almost double that in women; significantly larger absolute amounts were observed in men and African-Americans after adjustment first for stature, weight, and age; and >80% of within-gender or -ethnic group between-individual component variation was explained by stature, weight, age, gender, and ethnicity differences; and 2) most of between-individual TBK variation could be explained by total appendicular skeletal muscle ( r 2 = 0.865), whereas age, gender, and ethnicity were small but significant additional covariates (total r 2 = 0.903). Our study supports the hypotheses that skeletal muscle is reduced in the elderly and that TBK provides a reasonable indirect assessment of skeletal muscle mass. These findings provide a foundation for investigating skeletal muscle mass in a wide range of health-related conditions.


Ceiba ◽  
2016 ◽  
Vol 54 (1) ◽  
pp. 50-58
Author(s):  
Robert P. Rhoads ◽  
Lance H. Baumgard ◽  
Lidan Zhao

At the onset of heat stress, cattle initiate a series of whole body adaptations in an effort to cope with and dissipate additional heat load. These include well-known physiological changes such as increased respiration rate and sweating rate and decreased feed intake. Environmentally induced hyperthermia in ruminants depresses production as a consequence of reduced feed intake but it is unclear how shifts in metabolism may further affect production performance and physiological acclimation. Our evidence indicates that cattle experiencing heat stress do not appear to engage metabolic and glucose-sparing adaptations consistent with their plane of nutrition. In this context, the liver is uniquely positioned to direct exogenously and endogenously derived nutrients for use by other metabolically active tissues such as the mammary gland and skeletal muscle. Despite the prominent role of the liver in whole-body metabolism, alterations in the molecular mechanisms leading to hepatic adaptation during heat challenge are unclear. We are using management tools and metabolic modifiers, such as bovine somatotropin, in an attempt to better understand and improve hepatic function during heat stress. Because a large proportion of an animal’s mass is comprised of skeletal muscle, alterations in skeletal muscle metabolism and function can have a profound impact on whole-animal energy metabolism and nutrient homeostasis especially during periods of stress.  We have initiated studies to understand how hyperthermia influences the set points of several metabolic pathways within skeletal muscle. It appears that during heat stress bovine skeletal muscle experiences mitochondrial dysfunction leading to impaired cellular energy status. Finally, investigations into adipose tissue metabolism demonstrate impaired lipolytic functions likely due to a refractory nature to adrenergic stimuli. Taken together, this may have broad implications for the reduced production and heat intolerance seen during heat stress especially if tissue(s) are not able to make necessary contributions to whole-body energy homeostasis. Accurately understanding the biological mechanism(s) by which thermal stress reduces animal performance is critical for developing novel approaches (i.e. genetic, managerial and nutritional) to preserve growth and lactation especially given the critical importance of nutrients, such as glucose, to animal production and well being in these situations.


2017 ◽  
Vol 312 (4) ◽  
pp. E282-E299 ◽  
Author(s):  
Colleen S. Deane ◽  
Daniel J. Wilkinson ◽  
Bethan E. Phillips ◽  
Kenneth Smith ◽  
Timothy Etheridge ◽  
...  

Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cachexia, COPD, and organ failure, via engendering favorable adaptations such as increased muscle mass and oxidative capacity. Therefore, it is important to consider the effects of established and novel effectors of muscle mass, function, and metabolism in relation to nutrition and exercise. To address this gap, in this review, we detail existing evidence surrounding the efficacy of a nonexhaustive list of macronutrient, micronutrient, and “nutraceutical” compounds alone and in combination with exercise in relation to skeletal muscle mass, metabolism (protein and fuel), and exercise performance (i.e., strength and endurance capacity). It has long been established that macronutrients have specific roles and impact upon protein metabolism and exercise performance, (i.e., protein positively influences muscle mass and protein metabolism), whereas carbohydrate and fat intakes can influence fuel metabolism and exercise performance. Regarding novel nutraceuticals, we show that the following ones in particular may have effects in relation to 1) muscle mass/protein metabolism: leucine, hydroxyl β-methylbutyrate, creatine, vitamin-D, ursolic acid, and phosphatidic acid; and 2) exercise performance: (i.e., strength or endurance capacity): hydroxyl β-methylbutyrate, carnitine, creatine, nitrates, and β-alanine.


2017 ◽  
Vol 29 (9) ◽  
pp. 1644-1648 ◽  
Author(s):  
Akio Morimoto ◽  
Tadashi Suga ◽  
Nobuaki Tottori ◽  
Michio Wachi ◽  
Jun Misaki ◽  
...  

2003 ◽  
Vol 284 (1) ◽  
pp. E193-E205 ◽  
Author(s):  
G. van Hall ◽  
M. Jensen-Urstad ◽  
H. Rosdahl ◽  
H.-C. Holmberg ◽  
B. Saltin ◽  
...  

To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed by 10 min of double poling and diagonal stride at 72–76% maximal O2 uptake. A high lactate appearance rate (Ra, 184 ± 17 μmol · kg−1 · min−1) but a low arterial lactate concentration (∼2.5 mmol/l) were observed during Continuous Arm + Leg despite a substantial net lactate release by the arm of ∼2.1 mmol/min, which was balanced by a similar net lactate uptake by the leg. Whole body and limb lactate oxidation during Continuous Arm + Leg was ∼45% at rest and ∼95% of disappearance rate and limb lactate uptake, respectively. Limb lactate kinetics changed multiple times when exercise mode was changed. Whole body glucose and glycerol turnover was unchanged during the different skiing modes; however, limb net glucose uptake changed severalfold. In conclusion, the arterial lactate concentration can be maintained at a relatively low level despite high lactate Ra during exercise with a large muscle mass because of the large capacity of active skeletal muscle to take up lactate, which is tightly correlated with lactate delivery. The limb lactate uptake during exercise is oxidized at rates far above resting oxygen consumption, implying that lactate uptake and subsequent oxidation are also dependent on an elevated metabolic rate. The relative contribution of whole body and limb lactate oxidation is between 20 and 30% of total carbohydrate oxidation at rest and during exercise under the various conditions. Skeletal muscle can change its limb net glucose uptake severalfold within minutes, causing a redistribution of the available glucose because whole body glucose turnover was unchanged.


2015 ◽  
Vol 308 (2) ◽  
pp. R105-R111 ◽  
Author(s):  
Wladimir M. Medeiros ◽  
Mari C. T. Fernandes ◽  
Diogo P. Azevedo ◽  
Flavia F. M. de Freitas ◽  
Beatriz C. Amorim ◽  
...  

Central cardiorespiratory and gas exchange limitations imposed by chronic obstructive pulmonary disease (COPD) impair ambulatory skeletal muscle oxygenation during whole body exercise. This investigation tested the hypothesis that peripheral factors per se contribute to impaired contracting lower limb muscle oxygenation in COPD patients. Submaximal neuromuscular electrical stimulation (NMES; 30, 40, and 50 mA at 50 Hz) of the quadriceps femoris was employed to evaluate contracting skeletal muscle oxygenation while minimizing the influence of COPD-related central cardiorespiratory constraints. Fractional O2 extraction was estimated by near-infrared spectroscopy (deoxyhemoglobin/myoglobin concentration; deoxy-[Hb/Mb]), and torque output was measured by isokinetic dynamometry in 15 nonhypoxemic patients with moderate-to-severe COPD (SpO2 = 94 ± 2%; FEV1 = 46.4 ± 10.1%; GOLD II and III) and in 10 age- and gender-matched sedentary controls. COPD patients had lower leg muscle mass than controls (LMM = 8.0 ± 0.7 kg vs. 8.9 ± 1.0 kg, respectively; P < 0.05) and produced relatively lower absolute and LMM-normalized torque across the range of NMES intensities ( P < 0.05 for all). Despite producing less torque, COPD patients had similar deoxy-[Hb/Mb] amplitudes at 30 and 40 mA ( P > 0.05 for both) and higher deoxy-[Hb/Mb] amplitude at 50 mA ( P < 0.05). Further analysis indicated that COPD patients required greater fractional O2 extraction to produce torque (i.e., ↑Δdeoxy-[Hb/Mb]/torque) relative to controls ( P < 0.05 for 40 and 50 mA) and as a function of NMES intensity ( P < 0.05 for all). The present data obtained during submaximal NMES of small muscle mass indicate that peripheral abnormalities contribute mechanistically to impaired contracting skeletal muscle oxygenation in nonhypoxemic, moderate-to-severe COPD patients.


2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Akira Nemoto ◽  
Toru Goyagi

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Elisa Benetti ◽  
Raffaella Mastrocola ◽  
Mara Rogazzo ◽  
Fausto Chiazza ◽  
Manuela Aragno ◽  
...  

Peroxisome Proliferator Activated Receptor (PPAR)-δagonists may serve for treating metabolic diseases. However, the effects of PPAR-δagonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δagonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δupregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δactivation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.


2017 ◽  
Vol 117 (8) ◽  
pp. 1181-1188 ◽  
Author(s):  
Hui-yuan Tian ◽  
Rui Qiu ◽  
Li-peng Jing ◽  
Zhan-yong Chen ◽  
Geng-dong Chen ◽  
...  

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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