scholarly journals The Effects of Calcium-β-Hydroxy-β-Methylbutyrate on Aging-Associated Apoptotic Signaling and Muscle Mass and Function in Unloaded but Nonatrophied Extensor Digitorum Longus Muscles of Aged Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Brian T. Bennett ◽  
Junaith S. Mohamed ◽  
Stephen E. Alway

Beta-hydroxy-beta-methylbutyrate (HMB), a naturally occurring leucine metabolite, has been shown to attenuate plantar flexor muscle loss and increase myogenic stem cell activation during reloading after a period of significant muscle wasting by disuse in old rodents. However, it was less clear if HMB would alter dorsiflexor muscle response to unloading or reloading when there was no significant atrophy that was induced by unloading. In this study, we tested if calcium HMB (Ca-HMB) would improve muscle function and alter apoptotic signaling in the extensor digitorum longus (EDL) of aged animals that were unloaded but did not undergo atrophy. The EDL muscle was unloaded for 14 days by hindlimb suspension (HS) in aged (34-36 mo.) male Fisher 344×Brown Norway rats. The rats were removed from HS and allowed normal cage ambulation for 14 days of reloading (R). Throughout the study, the rats were gavaged daily with 170 mg of Ca-HMB or water 7 days prior to HS, then throughout 14 days of HS and 14 days of recovery after removing HS. The animals’ body weights were significantly reduced by ~18% after 14 days of HS and continued to decline by ~22% during R as compared to control conditions; however, despite unloading, EDL did not atrophy by HS, nor did it increase in mass after R. No changes were observed in EDL twitch contraction time, force production, fatigue resistance, fiber cross-sectional area, or markers of nuclear apoptosis (myonuclei + satellite cells) after HS or R. While HS and R increased the proapoptotic Bax protein abundance, BCL-2 abundance was also increased as was the frequency of TUNEL-positive myonuclei and satellite cells, yet muscle mass and fiber cross-sectional area did not change and Ca-HMB treatment had no effect reducing apoptotic signaling. These data indicate that (i) increased apoptotic signaling preceded muscle atrophy or occurred without significant EDL atrophy and (ii) that Ca-HMB treatment did not improve EDL signaling, muscle mass, or muscle function in aged rats, when HS and R did not impact mass or function.

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Salaheddin Sharif ◽  
James M. Thomas ◽  
David A. Donley ◽  
Diana L. Gilleland ◽  
Daniel E. Bonner ◽  
...  

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune, inflammatory disease associated with cachexia (reduced muscle and increased fat). Although strength-training exercise has been used in persons with RA, it is not clear if it is effective for reducing cachexia. A 46-year-old woman was studied to determine: (i) if resistance exercise could reverse cachexia by improving muscle mass, fiber cross-sectional area, and muscle function; and (2) if elevated apoptotic signaling was involved in cachexia with RA and could be reduced by resistance training. A needle biopsy was obtained from the vastus lateralis muscle of the RA subject before and after 16 weeks of resistance training. Knee extensor strength increased by 13.6% and fatigue decreased by 2.8% Muscle mass increased by 2.1%. Average muscle fiber cross-sectional area increased by 49.7%, and muscle nuclei increased slightly after strength training from 0.08 to 0.12 nuclei/μm2. In addition, there was a slight decrease (1.6%) in the number of apoptotic muscle nuclei after resistance training. This case study suggests that resistance training may be a good tool for increasing the number of nuclei per fiber area, decreasing apoptotic nuclei, and inducing fiber hypertrophy in persons with RA, thereby slowing or reversing rheumatoid cachexia.


2021 ◽  
Author(s):  
Shaobo Li ◽  
Haoyong Yu ◽  
Pin Zhang ◽  
Yinfang Tu ◽  
Yunfeng Xiao ◽  
...  

OBJECTIVE <p>To<a> explore the potential relevance of muscle mass as a variable contributor to body mass index (BMI) on BMI limitations in predicting diabetes remission (DR) after Roux-en-Y gastric bypass (RYGB). </a></p> <p> </p> <p>RESEARCH DESIGN AND METHODS</p> <p>We evaluated the relationship between muscle mass and BMI in 501 patients with type 2 diabetes mellitus and overweight or obesity. Of which <a>186 patients who underwent R</a>YGB were <a>studied to determine the role of baseline muscle mass </a><a>and BMI </a>in predicting DR. Muscle mass was assessed by estimated fat-free mass index (eFFMI) and psoas cross-sectional area (CSA).</p> <p> </p> <p>RESULTS</p> <p>A non-linear relationship existed between psoas CSA and BMI, whereas psoas CSA showed a highly positive correlation with <a>eFFMI</a>. Baseline psoas CSA and eFFMI were better than BMI for predicting 1- and 5-year DR. </p> <p> </p> <p>CONCLUSIONS</p> <p><a>The </a><a>non-linear relationship between</a> muscle mass and BMI may <a>partially contribute to </a><a>BMI limitations in predicting DR</a> after RYGB. </p>


Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3057
Author(s):  
Chang-Mu Chen ◽  
Min-Ni Chung ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
Kuo-Cheng Lan

Arsenic is a toxic metalloid. Infants with a low birth-weight have been observed in areas with high-level arsenic in drinking water ranging from 463 to 1025 μg/L. A distal muscular atrophy side effect has been observed in acute promyelocytic leukemia patients treated with arsenic trioxide (As2O3) for therapy. The potential of As2O3 on muscle atrophy remains to be clarified. In this study, the myoatrophic effect of arsenic was evaluated in normal mice and sciatic nerve denervated mice exposed with or without As2O3 (0.05 and 0.5 ppm) in drinking water for 4 weeks. We found that both 0.05 and 0.5 ppm As2O3 increased the fasting plasma glucose level; but only 0.5 ppm arsenic exposure significantly decreased muscle mass, muscle endurance, and cross-sectional area of muscle fibers, and increased muscle Atrogin-1 protein expression in the normal mice. Both 0.05 and 0.5 ppm As2O3 also significantly enhanced the inhibitory effects on muscle endurance, muscle mass, and cross-sectional area of muscle fibers, and increased the effect on muscle Atrogin-1 protein expression in the denervated mice. These in vivo results suggest that inorganic arsenic at doses relevant to humans may possess myoatrophic potential.


2019 ◽  
Vol 22 (8) ◽  
pp. 721-728
Author(s):  
Laura H Rayhel ◽  
Jessica M Quimby ◽  
Eric M Green ◽  
Valerie J Parker ◽  
Shasha Bai

Objectives The aim of this study was to evaluate the intra- and inter-rater reliability of epaxial muscle cross-sectional area measurement on feline CT images and to determine the relationship between normalized epaxial muscle area (EMA) and subjective muscle condition score (MCS). Methods Feline transverse CT images including the junction of the 13th thoracic vertebrae/13th rib head were retrospectively reviewed. Right and left epaxial muscle circumference and vertebral body height were measured and an average normalized EMA (ratio of epaxial area:vertebral height) was calculated for each image. Measurements were performed by three individuals blinded to the clinical data and were repeated 1 month later. Intra- and inter-rater reliability of EMA was assessed with concordance correlation coefficient (CCC), and Bland–Altman analysis was performed to assess bias and limits of agreement (LoA) between and within observers at different time points. In cats for which MCS data were available, EMA was compared between differing MCSs via the Kruskal–Wallis test, with Bonferroni-corrected Wilcoxon rank-sum post-hoc analysis. Results In total, 101 CT scans met the inclusion criteria for reliability analysis, 29 of which had muscle condition information available for analysis. Intra-rater EMA CCC ranged from 0.84 to 0.99 with minimal bias (range –0.16 to 0.08) and narrow LoA. Inter-rater EMA CCC ranged from 0.87 to 0.94, bias was larger (range –0.46 to 0.66) and LoA were wider when assessed between observers. Median EMA was significantly lower in cats with severe muscle atrophy (2.76, range 1.28–3.96) than in all other MCS groups ( P <0.0001 for all comparisons). Conclusions and relevance Measurement of EMA on CT showed strong intra-rater reliability, and median EMA measurements were significantly lower in cats with severe muscle wasting, as assessed on physical examination. Further studies correlating EMA to lean muscle mass in cats are needed to determine whether this method may be useful to quantify muscle mass in patients undergoing a CT scan.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  

222 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. Androgen deprivation therapy (ADT) has been shown to result in muscle wasting in prostate cancer pts. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential pts who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 pts were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, pts lost an average of 1.9 kg ± 1.9 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (−0.80 ± 1.71, p = 0.18) and total non-adipose mass (−1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (−0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in pts with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.


2010 ◽  
Vol 298 (1) ◽  
pp. C149-C162 ◽  
Author(s):  
Nadège Zanou ◽  
Georges Shapovalov ◽  
Magali Louis ◽  
Nicolas Tajeddine ◽  
Chiara Gallo ◽  
...  

Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu , excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC)1 ion channel in this entry of Ca2+and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1−/−mice. The influx of Ca2+through TRPC1 channels represents a minor part of the entry of Ca2+into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+concentration ([Ca2+]i) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1−/−mice stimulated repeatedly progressively display lower [Ca2+]itransients than those observed in TRPC1+/+fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1−/−mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1−/−mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca2+during repeated contractions and help muscles to maintain their force during sustained repeated contractions.


2011 ◽  
Vol 111 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Christopher L. Mendias ◽  
Erdan Kayupov ◽  
Joshua R. Bradley ◽  
Susan V. Brooks ◽  
Dennis R. Claflin

Myostatin ( MSTN) is a member of the transforming growth factor-β superfamily of cytokines and is a negative regulator of skeletal muscle mass. Compared with MSTN+/+ mice, the extensor digitorum longus muscles of MSTN−/− mice exhibit hypertrophy, hyperplasia, and greater maximum isometric force production (Fo), but decreased specific maximum isometric force (sFo; Fo normalized by muscle cross-sectional area). The reason for the reduction in sFo was not known. Studies in myotubes indicate that inhibiting myostatin may increase muscle mass by decreasing the expression of the E3 ubiquitin ligase atrogin-1, which could impact the force-generating capacity and size of muscle fibers. To gain a greater understanding of the influence of myostatin on muscle contractility, we determined the impact of myostatin deficiency on the contractility of permeabilized muscle fibers and on the levels of atrogin-1 and ubiquitinated myosin heavy chain in whole muscle. We hypothesized that single fibers from MSTN−/− mice have a greater Fo, but no difference in sFo, and a decrease in atrogin-1 and ubiquitin-tagged myosin heavy chain levels. The results indicated that fibers from MSTN−/− mice have a greater cross-sectional area, but do not have a greater Fo and have a sFo that is significantly lower than fibers from MSTN+/+ mice. The extensor digitorum longus muscles from MSTN−/− mice also have reduced levels of atrogin-1 and ubiquitinated myosin heavy chain. These findings suggest that myostatin inhibition in otherwise healthy muscle increases the size of muscle fibers and decreases atrogin-1 levels, but does not increase the force production of individual muscle fibers.


2005 ◽  
Vol 99 (3) ◽  
pp. 1085-1092 ◽  
Author(s):  
Nobuo Yasuda ◽  
Elisa I. Glover ◽  
Stuart M. Phillips ◽  
Robert J. Isfort ◽  
Mark A. Tarnopolsky

The purpose of this study was to determine the effects of short-term (14-day) unilateral leg immobilization using a simple knee brace (60° flexion)- or crutch-mediated model on muscle function and morphology in men (M, n = 13) and women (W, n = 14). Isometric and isokinetic (concentric-slow, 0.52 rad/s and fast, 5.24 rad/s) knee extensor peak torque was determined at three time points (Pre, Day-2, and Day-14). At the same time points, magnetic resonance imaging was used to measure the cross-sectional area of the quadriceps femoris and dual-energy X-ray absorptiometry scanning was used to calculate leg lean mass. Muscle biopsies were taken from vastus lateralis at Pre and Day-14 for myosin ATPase and myosin heavy chain analysis. Women showed greater decreases (Pre vs. Day-14) compared with men in specific strength (N/cm2) for isometric [M = 3.1 ± 13.3, W = 17.1 ± 15.9%; P = 0.055 (mean ± SD)] and concentric-slow (M = 4.7 ± 11.3, W = 16.6 ± 18.4%; P < 0.05) contractions. There were no immobilization-induced sex-specific differences in the decrease in quadriceps femoris cross-sectional area (M = 5.7 ± 5.0, W = 5.9 ± 5.2%) or leg lean mass (M = 3.7 ± 4.2, W = 2.7 ± 2.8%). There were no fiber-type transformations, and the decreases in type I (M = 4.8 ± 5.0, W = 5.9 ± 3.4%), IIa (M = 7.9 ± 9.9, W = 8.8 ± 8.0%), and IIx (M = 10.7 ± 10.8, W = 10.8 ± 12.1%) fiber areas were similar between sexes. These findings indicate that immobilization-induced loss of knee extensor muscle strength is greater in women compared with men despite a similar extent of atrophy at the myofiber and whole muscle levels after 14 days of unilateral leg immobilization. Furthermore, we have described an effective and safe knee immobilization method that results in reductions in quadriceps muscle strength and size.


1990 ◽  
Vol 259 (1) ◽  
pp. C92-C102 ◽  
Author(s):  
S. E. Alway ◽  
W. J. Gonyea ◽  
M. E. Davis

The contributions of fiber hypertrophy and new fiber formation to the onset of stretch-induced muscle enlargement were evaluated in the anterior latissimus dorsi (ALD) of adult Japanese quails, because it was not known whether the mechanisms which initiate new fiber formation were dependent on first achieving significant fiber hypertrophy. A weight corresponding to 10% of the bird's body mass was attached to one wing, and eight birds were killed after each day during the first week of stretch. Muscle mass was significantly increased after 48 h of stretch; however, the elevation in nonmuscle tissue accounted for this increase. Muscle mass corrected for non-muscle tissue was significantly greater than the intra-animal control by the fourth day of stretch. Mean fiber cross-sectional area did not change during days 0-6, but cross-sectional area was 30.0 +/- 17.2% greater than the intra-animal control areas at day 7. Fiber number determined after nitric acid digestion of connective tissue was 27.1 +/- 5.8% greater than the intra-animal control at days 5-7 of stretch, but the number of fibers in the control muscles at days 5 and 6 were lower than at day 0. Thus new fiber formation was not preceded by significant fiber hypertrophy. These results fail to support a mechanism for new fiber formation which involves fiber splitting from hypertrophied myofibers during the first week of stretch.


2008 ◽  
Vol 16 (3) ◽  
pp. 259 ◽  
Author(s):  
M. RUUSUNEN ◽  
E. PUOLANNE ◽  
K. PARTANEN

One of the aims in domestic pig breeding has been to increase the size of litters resulting in variation in birth weight of piglets. Pig breeding has also resulted in increased body muscle mass. Muscles with the same size can consist either of large number of thin muscle fibres or small number of thick muscle fibres. Larger body muscle content means that in living animal the heart must pump blood to larger muscle mass than earlier. Our interest in this study was to investigate the relationship between the pig’s birth weight and (i) growth performance and carcass composition, (ii) the size of organs, and (iii) the mean muscle fibre cross-sectional area at slaughter. The study consisted of twenty pigs slaughtered at the age of 165±2 days. The day after the slaughter, the carcass composition was determined by dissecting the chilled carcass into lean, fat, bones, and skin and organs were weighed. The average cross sectional area of muscle fibres was determined from three fast-twitch muscles longissimus dorsi, semimembranosus, gluteus superficialis, and two slow-twitch muscles infraspinatus and masseter. The birth weight of pigs ranged from 0.9 to 2.2 kg. We found no clear relationships between the birth weight and the pig’s growth performance from birth to slaughter. When the birth weight increased the heart weight at slaughter increased as well (P < 0.01). The heart weight was higher in those pigs with high carcass weight (P < 0.05) and with the high weight of total muscle mass in the carcass (P < 0.001). The cross sectional area of muscle fibres in M. longissimus dorsi (P < 0.05), M. semimembranosus (P < 0.10), and M. gluteus superficialis (P < 0.05) was larger in those pigs with low birth weight compared to those found in pigs with high birth weight.;


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