scholarly journals Maintenance of muscle mass in adult male mice is independent of testosterone

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0240278
Author(s):  
Arik Davidyan ◽  
Suraj Pathak ◽  
Keith Baar ◽  
Sue C. Bodine

Testosterone is considered a potent anabolic agent in skeletal muscle with a well-established role in adolescent growth and development in males. However, the role of testosterone in the regulation of skeletal muscle mass and function throughout the lifespan has yet to be fully established. While some studies suggest that testosterone is important for the maintenance of skeletal muscle mass, an understanding of the role this hormone plays in young, adult, and old males with normal and low serum testosterone levels is lacking. We investigated the role testosterone plays in the maintenance of muscle mass by examining the effect of orchiectomy-induced testosterone depletion in C57Bl6 male mice at ages ranging from early postnatal through old age (1.5-, 5-, 12-, and 24-month old mice). Following 28 days of testosterone depletion, we assessed mass and fiber cross-sectional-area (CSA) of the tibialis anterior, gastrocnemius, and quadriceps muscles. In addition, we measured global rates of protein synthesis and degradation using the SuNSET method, western blots, and enzyme activity assays. Twenty-eight days of testosterone depletion resulted in reduced muscle mass in the two youngest cohorts, but had no effect in the two oldest cohorts. Mean CSA decreased only in the youngest cohort and only in the tibialis anterior muscle. Testosterone depletion resulted in a general increase in proteasome activity at all ages. No change in protein synthesis was detected at the terminal time point. These data suggest that within physiological serum concentrations, testosterone may not be critical for the maintenance of muscle mass in mature male mice; however, in young mice testosterone is crucial for normal growth.

2020 ◽  
Author(s):  
Arik Davidyan ◽  
Keith Baar ◽  
Sue C. Bodine

AbstractTestosterone is considered a potent anabolic agent in skeletal muscle with a well-established role in adolescent growth and development in males. However, alterations in the role of testosterone in the regulation of skeletal muscle mass and function throughout the lifespan has yet to be established. While some studies suggest that testosterone is important for the maintenance of skeletal muscle mass, an understanding of the role this hormone plays in young, adult, and old males with normal and low serum testosterone levels is lacking. We investigated the role testosterone plays in the maintenance of muscle mass by examining the effect of orchiectomy-induced testosterone depletion in C57Bl6 male mice at ages ranging from early postnatal through old age; the age groups we used included 1.5-, 5-, 12-, and 24-month old mice. Following 28 days of testosterone depletion, we assessed mass and fiber cross-sectional-area (CSA) of the tibialis anterior, gastrocnemius, and quadriceps muscles. In addition, we measured global rates of protein synthesis and degradation using the SuNSET method, western blots, and enzyme activity assays. 28 days of testosterone depletion resulted in smaller muscle mass in the two youngest cohorts but had no effect in the two older ones. Mean CSA decreased only in the youngest cohort and only in the tibialis anterior muscle. Testosterone depletion resulted in a general increase in proteasome activity at all ages. We did not detect changes in protein synthesis at the terminal time point. This data suggest that within physiological serum concentrations, testosterone is not important for the maintenance of muscle mass in mature male mice; however, in young mice testosterone is crucial for normal growth.


2014 ◽  
Vol 307 (11) ◽  
pp. E983-E993 ◽  
Author(s):  
Florian A. Britto ◽  
Gwenaelle Begue ◽  
Bernadette Rossano ◽  
Aurélie Docquier ◽  
Barbara Vernus ◽  
...  

REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy.


Author(s):  
Marcus M. Lawrence ◽  
Kevin A. Zwetsloot ◽  
Susan T. Arthur ◽  
Chase A. Sherman ◽  
Joshua R. Huot ◽  
...  

Skeletal muscle mass and strength are lost with aging. Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase protein synthesis in C2C12 skeletal muscle cells and muscle strength in young rats. The objective of this study was to determine whether an extract from Ajuga turkestanica (ATE), enriched in phytoecdysteroids, and 20E affect skeletal muscle mass and fiber size, fiber type, activation of the PI3K–Akt signaling pathway, and the mRNA levels of MAFbx, MuRF-1, and myostatin in sedentary aging mice. Aging male C57BL/6 mice (20 months old) received ATE, 20E, or vehicle (CT) once per day for 28 days or a single acute dose. Treatment did not alter body, muscle, or organ mass; fiber cross-sectional area; or fiber type in the triceps brachii or plantaris muscles. Likewise, protein synthesis signaling markers (i.e., phosphorylation of AktSer473 and p70S6kThr389) measured after either 28 days or acutely were unchanged. Neither ATE nor 20E treatment for 28 days affected the mRNA levels of MAFbx, MuRF-1, and myostatin. In conclusion, these data indicate that phytoecdysteroid treatment does not alter muscle mass or fiber type, nor does it activate protein synthesis signaling in the skeletal muscle of sedentary aging mice.


2013 ◽  
Author(s):  
Naeyer Helene De ◽  
Inge Everaert ◽  
Spaey Annelies De ◽  
Jean-Marc Kaufman ◽  
Youri Taes ◽  
...  

2016 ◽  
Vol 41 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Jameason D. Cameron ◽  
Ronald J. Sigal ◽  
Glen P. Kenny ◽  
Angela S. Alberga ◽  
Denis Prud’homme ◽  
...  

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.


2003 ◽  
Vol 285 (4) ◽  
pp. E876-E888 ◽  
Author(s):  
Suzanne Reisz-Porszasz ◽  
Shalender Bhasin ◽  
Jorge N. Artaza ◽  
Ruoqing Shen ◽  
Indrani Sinha-Hikim ◽  
...  

Mutations in the myostatin gene are associated with hypermuscularity, suggesting that myostatin inhibits skeletal muscle growth. We postulated that increased tissue-specific expression of myostatin protein in skeletal muscle would induce muscle loss. To investigate this hypothesis, we generated transgenic mice that overexpress myostatin protein selectively in the skeletal muscle, with or without ancillary expression in the heart, utilizing cDNA constructs in which a wild-type (MCK/Mst) or mutated muscle creatine kinase (MCK-3E/Mst) promoter was placed upstream of mouse myostatin cDNA. Transgenic mice harboring these MCK promoters linked to enhanced green fluorescent protein (EGFP) expressed the reporter protein only in skeletal and cardiac muscles (MCK) or in skeletal muscle alone (MCK-3E). Seven-week-old animals were genotyped by PCR of tail DNA or by Southern blot analysis of liver DNA. Myostatin mRNA and protein, measured by RT-PCR and Western blot, respectively, were significantly higher in gastrocnemius, quadriceps, and tibialis anterior of MCK/Mst-transgenic mice compared with wild-type mice. Male MCK/Mst-transgenic mice had 18–24% lower hind- and forelimb muscle weight and 18% reduction in quadriceps and gastrocnemius fiber cross-sectional area and myonuclear number (immunohistochemistry) than wild-type male mice. Male transgenic mice with mutated MCK-3E promoter showed similar effects on muscle mass. However, female transgenic mice with either type of MCK promoter did not differ from wild-type controls in either body weight or skeletal muscle mass. In conclusion, increased expression of myostatin in skeletal muscle is associated with lower muscle mass and decreased fiber size and myonuclear number, decreased cardiac muscle mass, and increased fat mass in male mice, consistent with its role as an inhibitor of skeletal muscle mass. The mechanism of gender specificity remains to be clarified.


2017 ◽  
Vol 135 (5) ◽  
pp. 434-443 ◽  
Author(s):  
Ricardo Aurélio Carvalho Sampaio ◽  
Priscila Yukari Sewo Sampaio ◽  
Luz Albany Arcila Castaño ◽  
João Francisco Barbieri ◽  
Hélio José Coelho Júnior ◽  
...  

2015 ◽  
Vol 114 (11) ◽  
pp. 1838-1844 ◽  
Author(s):  
Min Jung Ko ◽  
Sungha Yun ◽  
Kyungwon Oh ◽  
Kirang Kim

AbstractThe objective of this study was to examine whether high serum 25-hydroxyvitamin D (25(OH)D) concentration was associated with high skeletal muscle mass, taking into account the effects of sex and age among the participants of the Korea National Health and Nutrition Examination Survey (KNHANES) aged 40 years or older. This was a cross-sectional study using data from the 2009 to 2010 KNHANES; a total of 8406 subjects (3671 men and 4735 women) were included. The appendicular skeletal muscle mass index (ASMMI, kg/m2) was estimated to measure the skeletal muscle mass. Hypovitaminosis was classified when the level of serum 25(OH)D was <20 ng/ml. The general linear model adjusted for confounding factors was used to determine differences in means of ASMMI by 25(OH)D status. The mean values of ASMMI were higher for men when compared with women. Women had a greater proportion of hypovitaminosis (71·1 %) compared with men (53·2 %). After adjusting for multiple factors, men were seen to have significant differences in ASMMI based on 25(OH)D status regardless of age, showing a lower mean value of ASSMI in those with hypovitaminosis. However, there was no difference in ASMMI by 25(OH)D status among women in both younger and older age groups. In conclusion, we found that there might be a positive relationship between 25(OH)D and skeletal muscle mass in men, indicating that interventions to improve 25(OH)D levels that are aimed at increasing muscle mass could be beneficial for men with more rapid decreased rate of skeletal muscle mass.


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.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tatiana de Paula ◽  
Mauren de Freitas ◽  
Vanessa Lopes ◽  
Maria Elisa Miller ◽  
Karen Araujo ◽  
...  

Abstract Objectives The aim of the study was to establish the prevalence of sarcopenia and associated factors in elderly with type 2 diabetes (DM) in southern Brazil. Methods A cross-sectional study was performed in 240 patients with type 2 DM. The diagnosis of sarcopenia was performed according to EWGSOP criteria. Muscle mass was calculated by skeletal muscle mass index (appendicular skeletal muscle mass/height² - Inbody® bioimpendance). Muscle strength was assessed by manual grip strength (Jamar® dynamometer) and physical performance was assessed by the sit and lift test. Patients with type 2 DM with age ≥60 years and with the ability to ambulate were selected. Patients with recent cardiovascular events, serum creatinine >2.0 mg/dl, use of corticosteroids and BMI >40 kg/m² were excluded. The sample size was 240 patients based on meta-analysis who found 17% sarcopenia in elderly patients without DM. Results We included 240 patients aged 68.4 ± 5.5 years, 53.2% were women and the duration of DM was 15 (8–22) years, the BMI was 29.4 ± 4.4 kg/m². The prevalence of sarcopenia was 21% and men had more sarcopenia (75%). Patients with sarcopenia walk less [3541 (2227–4574) vs. 4521 (3037–5678) steps, P = 0.013], drink more alcohol [21 (56.8%) vs. 71 (31.8%); P < 0.034] and have lower total cholesterol levels [146 ± 41 Vs. 168 ± 43; P = 0.007] than the group without sarcopenia. In multivariate logistic regression models, walking < 3760 steps [OR = 2868; CI 95% 1.331–6.181] and male [OR = 5285; CI 95% 2261–12,350], were associated with sarcopenia. Conclusions The prevalence of sarcopenia was 21%, higher than in patients without diabetes (17%). In this group of patients, lower physical activity, and male sex were associated with sarcopenia. Funding Sources FIPE n. 160467; CAPES.


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