Estrogen status and skeletal muscle recovery from disuse atrophy

Although estrogen loss can alter skeletal muscle recovery from disuse, the specific components of muscle regrowth that are estrogen sensitive have not been described. The primary purpose of this study was to determine the components of skeletal muscle mass recovery that are biological targets of estrogen. Intact, ovariectomized (OVX), and ovariectomized with 17β-estradiol replacement (OVX+E2) female rats were subjected to hindlimb suspension for 10 days and then returned to normal cage ambulation for the duration of recovery. Soleus muscle mass returned to control levels by day 7 of recovery in the intact animals, whereas OVX soleus mass did not recover until day 14. Intact rats recovered soleus mean myofiber cross-sectional area (CSA) by day 14 of recovery, whereas the OVX soleus remained decreased (42%) at day 14. OVX mean fiber CSA did return to control levels by day 28 of recovery. The OVX+E2 treatment group recovered mean CSA at day 14, as in the intact animals. Myofibers demonstrating central nuclei were increased at day 14 in the OVX group, but not in intact or OVX+E2 animals. The percent noncontractile tissue was also increased 29% in OVX muscle at day 14, but not in either intact or OVX+E2 groups. In addition, collagen 1a mRNA was increased 45% in OVX muscle at day 14 of recovery. These results suggest that myofiber growth, myofiber regeneration, and extracellular matrix remodeling are estrogen-sensitive components of soleus muscle mass recovery from disuse atrophy.

Download Full-text

High-Molecular-Weight Polyphenol-Rich Fraction of Black Tea Does Not Prevent Atrophy by Unloading, But Promotes Soleus Muscle Mass Recovery from Atrophy in Mice

Nutrients ◽

10.3390/nu11092131 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2131 ◽

Cited By ~ 1

Author(s):

Yuki Aoki ◽

Tetsuo Ozawa ◽

Osamu Numata ◽

Tohru Takemasa

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Soleus Muscle ◽

Mammalian Target Of Rapamycin ◽

Black Tea ◽

Normal Diet ◽

Hindlimb Suspension ◽

Ribosomal Protein S6 ◽

Disuse Muscle Atrophy ◽

Mass Recovery

Previously, we reported that polyphenol-rich fraction (named E80) promotes skeletal muscle hypertrophy induced by functional overload in mice. This study indicates that E80 has potential for affecting skeletal muscle mass. Then, we evaluate the effect of E80 on atrophic and recovery conditions of skeletal muscle in mice. Hindlimb suspension (unloading) and relanding (reloading) are used extensively to observe disuse muscle atrophy and subsequent muscle mass recovery from atrophy. Eight-week old C57BL/6 mice were fed either a normal diet or a diet containing 0.5% E80 for two weeks under conditions of hindlimb suspension and a subsequent 5 or 10 days of reloading. We found that E80 administration did not prevent atrophy during hindlimb suspension, but promoted recovery of slow-twitch (soleus) muscle mass from atrophy induced by hindlimb suspension. After five days of reloading, we discovered that phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt and P70 ribosomal protein S6 kinase (S6K), was activated in the muscle. Therefore, E80 administration accelerated mTOR signal and increased protein synthesis in the reloaded soleus muscle.

Download Full-text

β-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice

Nutrients ◽

10.3390/nu12082180 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2180

Author(s):

Mari Noguchi ◽

Tomoya Kitakaze ◽

Yasuyuki Kobayashi ◽

Katsuyuki Mukai ◽

Naoki Harada ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Soleus Muscle ◽

Muscle Fibers ◽

Skeletal Muscle Atrophy ◽

Related Factor ◽

Related Factors ◽

Cross Sectional ◽

Senescence Accelerated Mouse

We investigated the effects of β-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or β-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. β-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, β-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, β-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. β-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, β-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the β-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that β-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

Download Full-text

Testosterone suppression does not exacerbate disuse atrophy and impairs muscle recovery that is not rescued by high protein

Journal of Applied Physiology ◽

10.1152/japplphysiol.00752.2019 ◽

2020 ◽

Vol 129 (1) ◽

pp. 5-16 ◽

Cited By ~ 2

Author(s):

Erik D. Hanson ◽

Andrew C. Betik ◽

Cara A. Timpani ◽

John Tarle ◽

Xinmei Zhang ◽

...

Keyword(s):

Skeletal Muscle ◽

Adverse Effects ◽

Muscle Mass ◽

Caloric Intake ◽

Disuse Atrophy ◽

Muscle Recovery ◽

Testosterone Levels ◽

Muscle Disuse ◽

Low Testosterone ◽

And Function

Low testosterone levels during skeletal muscle disuse did not worsen declines in muscle mass and function, although hypogonadism may attenuate recovery during subsequent reloading. Diets high in casein did not improve outcomes during immobilization or reloading. Practical strategies are needed that do not compromise caloric intake yet provide effective protein doses to augment these adverse effects.

Download Full-text

Reversal of deficits in aged skeletal muscle during disuse and recovery in response to treatment with a secrotome product derived from partially differentiated human pluripotent stem cells

GeroScience ◽

10.1007/s11357-021-00423-0 ◽

2021 ◽

Author(s):

Dennis K. Fix ◽

Ziad S. Mahmassani ◽

Jonathan J. Petrocelli ◽

Naomi M.M.P. de Hart ◽

Patrick J. Ferrara ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Horse Serum ◽

Hindlimb Unloading ◽

Response To Treatment ◽

C2c12 Myotubes ◽

Transcriptional Networks ◽

Matrix Remodeling ◽

Disuse Atrophy ◽

Experimental Conditions

AbstractAged individuals are at risk to experience slow and incomplete muscle recovery following periods of disuse atrophy. While several therapies have been employed to mitigate muscle mass loss during disuse and improve recovery, few have proven effective at both. Therefore, the purpose of this study was to examine the effectiveness of a uniquely developed secretome product (STEM) on aged skeletal muscle mass and function during disuse and recovery. Aged (22 months) male C57BL/6 were divided into PBS or STEM treatment (n = 30). Mice within each treatment were assigned to either ambulatory control (CON; 14 days of normal cage ambulation), 14 days of hindlimb unloading (HU), or 14 days of hindlimb unloading followed by 7 days of recovery (recovery). Mice were given an intramuscular delivery into the hindlimb muscle of either PBS or STEM every other day for the duration of their respective treatment group. We found that STEM-treated mice compared to PBS had greater soleus muscle mass, fiber cross-sectional area (CSA), and grip strength during CON and recovery experimental conditions and less muscle atrophy and weakness during HU. Muscle CD68 +, CD11b + and CD163 + macrophages were more abundant in STEM-treated CON mice compared to PBS, while only CD68 + and CD11b + macrophages were more abundant during HU and recovery conditions with STEM treatment. Moreover, STEM-treated mice had lower collagen IV and higher Pax7 + cell content compared to PBS across all experimental conditions. As a follow-up to examine the cell autonomous role of STEM on muscle, C2C12 myotubes were given STEM or horse serum media to examine myotube fusion/size and effects on muscle transcriptional networks. STEM-treated C2C12 myotubes were larger and had a higher fusion index and were related to elevated expression of transcripts associated with extracellular matrix remodeling. Our results demonstrate that STEM is a unique cocktail that possesses potent immunomodulatory and cytoskeletal remodeling properties that may have translational potential to improve skeletal muscle across a variety of conditions that adversely effect aging muscle.

Download Full-text

Mature IGF-I excels in promoting functional muscle recovery from disuse atrophy compared with pro-IGF-IA

Journal of Applied Physiology ◽

10.1152/japplphysiol.00955.2013 ◽

2014 ◽

Vol 116 (7) ◽

pp. 797-806 ◽

Cited By ~ 11

Author(s):

SooHyun Park ◽

Becky K. Brisson ◽

Min Liu ◽

Janelle M. Spinazzola ◽

Elisabeth R. Barton

Keyword(s):

Skeletal Muscle ◽

Force Production ◽

Hindlimb Suspension ◽

Strength Analysis ◽

Disuse Atrophy ◽

Fiber Morphology ◽

Muscle Recovery ◽

Igf I ◽

Suspension Model ◽

Muscle Force Production

Prolonged disuse of skeletal muscle results in atrophy, and once physical activity is resumed, there is increased susceptibility to injury. Insulin-like growth factor-I (IGF-I) is considered a potential therapeutic target to attenuate atrophy during unloading and to enhance rehabilitation upon reloading of skeletal muscles, due to its multipronged actions on satellite cell proliferation, differentiation, and survival, as well as its actions on muscle fibers to boost protein synthesis and inhibit protein degradation. However, the form of IGF-I delivered may alter the success of treatment. Using the hindlimb suspension model of disuse atrophy, we compared the efficacy of two IGF-I forms in protection against atrophy and enhancement of recovery: mature IGF-I (IGF-IS) lacking the COOH-terminal extension, called the E-peptide, and IGF-IA, which is the predominant form retaining the E-peptide. Self-complementary adeno-associated virus harboring the murine Igf1 cDNA constructs were delivered to hindlimbs of adult female C57BL6 mice 3 days prior to hindlimb suspension. Hindlimb muscles were unloaded for 7 days and then reloaded for 3, 7, and 14 days. Loss of muscle mass following suspension was not prevented by either IGF-I construct. However, IGF-IS expression maintained soleus muscle force production. Further, IGF-IS treatment caused rapid recovery of muscle fiber morphology during reloading and maintained muscle strength. Analysis of gene expression revealed that IGF-IS expression accelerated the downregulation of atrophy-related genes compared with untreated or IGF-IA-treated samples. We conclude that mature-IGF-I may be a better option than pro-IGF-IA to promote skeletal muscle recovery following disuse atrophy.

Download Full-text

Age-related differences in apoptosis with disuse atrophy in soleus muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00576.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. R1288-R1296 ◽

Cited By ~ 137

Author(s):

Christiaan Leeuwenburgh ◽

Cathy M. Gurley ◽

Beau A. Strotman ◽

Esther E. Dupont-Versteegden

Keyword(s):

Skeletal Muscle ◽

Soleus Muscle ◽

Caspase 3 ◽

Cross Sectional Area ◽

Disuse Atrophy ◽

Sectional Area ◽

Cross Sectional ◽

Age Related ◽

Old Rats ◽

Subsarcolemmal Mitochondria

Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 × Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant ( P = 0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS.

Download Full-text

Beneficial effects of cod protein on skeletal muscle repair following injury

Applied Physiology Nutrition and Metabolism ◽

10.1139/h2012-021 ◽

2012 ◽

Vol 37 (3) ◽

pp. 489-498 ◽

Cited By ~ 15

Author(s):

Junio Dort ◽

Amélie Sirois ◽

Nadine Leblanc ◽

Claude H. Côté ◽

Hélène Jacques

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Tibialis Anterior Muscle ◽

Muscle Growth ◽

Peanut Protein ◽

Muscle Repair ◽

Post Injury ◽

Cross Sectional ◽

Resolution Of Inflammation ◽

Mass Recovery

This study examined the effect of peanut and cod proteins on post-damage skeletal muscle repair, compared with casein. We hypothesized that because of their high arginine content, these proteins would improve the resolution of inflammation and muscle mass recovery following injury. One hundred and twenty-eight male Wistar rats were assigned to isoenergetic diets composed of casein and peanut (experiment 1) or cod protein (experiment 2). After 21 days of feeding, one tibialis anterior muscle (TA) was injured with bupivacaine, while the contralateral TA was injected with saline (sham muscle). Measurements were taken at days 0, 3, 14, and 24 post-injury. Compared with casein, peanut protein reduced muscle mass at days 0 (–12%, p = 0.005) and 14 post-injury in the injured muscle (–13%, p = 0.04), and lowered myofiber cross-sectional area in both the sham (–21%, p = 0.008) and injured muscles (–26%, p = 0.05) at day 24 post-injury, showing that peanut protein has a weak potential to support muscle growth. At day 14 post-injury, muscle mass in the sham (13%, p = 0.02) and injured muscles (12%, p = 0.01) was higher in cod-protein-fed rats, indicating better muscle mass recovery, than in casein-fed rats. Cod protein tended (p = 0.06) to decrease the density of neutrophils (–24%) at day 14 post-injury in the injured muscle, and to decrease the density of ED1+ macrophages at day 24 post-injury in both sham (–29%, p = 0.03) and injured (–40%, p = 0.01) muscles. No effects were observed for peanut protein. These data indicate that cod protein is better for promoting growth and regeneration of skeletal muscle after trauma, partly because of the improved resolution of inflammation.

Download Full-text

Body composition and energy intake — skeletal muscle mass is the strongest predictor of food intake in obese adolescents: The HEARTY trial

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0479 ◽

2016 ◽

Vol 41 (6) ◽

pp. 611-617 ◽

Cited By ~ 37

Author(s):

Jameason D. Cameron ◽

Ronald J. Sigal ◽

Glen P. Kenny ◽

Angela S. Alberga ◽

Denis Prud’homme ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Composition ◽

Body Weight ◽

Muscle Mass ◽

Energy Intake ◽

Skeletal Muscle Mass ◽

Fat Free Mass ◽

Cross Sectional ◽

Percentage Body Fat ◽

Obese Adolescents

There has been renewed interest in examining the relationship between specific components of energy expenditure and the overall influence on energy intake (EI). The purpose of this cross-sectional analysis was to determine the strongest metabolic and anthropometric predictors of EI. It was hypothesized that resting metabolic rate (RMR) and skeletal muscle mass would be the strongest predictors of EI in a sample of overweight and obese adolescents. 304 post-pubertal adolescents (91 boys, 213 girls) aged 16.1 (±1.4) years with body mass index at or above the 95th percentile for age and sex OR at or above the 85th percentile plus an additional diabetes risk factor were measured for body weight, RMR (kcal/day) by indirect calorimetry, body composition by magnetic resonance imaging (fat free mass (FFM), skeletal muscle mass, fat mass (FM), and percentage body fat), and EI (kcal/day) using 3 day food records. Body weight, RMR, FFM, skeletal muscle mass, and FM were all significantly correlated with EI (p < 0.005). After adjusting the model for age, sex, height, and physical activity, only FFM (β = 21.9, p = 0.007) and skeletal muscle mass (β = 25.8, p = 0.02) remained as significant predictors of EI. FFM and skeletal muscle mass also predicted dietary protein and fat intake (p < 0.05), but not carbohydrate intake. In conclusion, with skeletal muscle mass being the best predictor of EI, our results support the hypothesis that the magnitude of the body’s lean tissue is related to absolute levels of EI in a sample of inactive adolescents with obesity.

Download Full-text