scholarly journals Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat

2017 ◽  
Vol 232 (3) ◽  
pp. 561-572 ◽  
Author(s):  
Ganga Gokulakrishnan ◽  
Xiaoyan Chang ◽  
Ryan Fleischmann ◽  
Marta L Fiorotto
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Progenitor Cell ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Pregnant Rats ◽  
Cross Sectional ◽  
Muscle Progenitor Cell ◽  
Fetal Muscle

Perinatal skeletal muscle growth rates are a function of protein and myonuclear accretion. Precocious exposure of the fetus to glucocorticoids (GLC) in utero impairs muscle growth. Reduced muscle protein synthesis rates contribute to this response, but the consequences for myonuclear hyperplasia are unknown. To test the hypothesis that blunting of Pax7+ muscle progenitor cell proliferative activity by GLC in vivo also contributes to reduced fetal muscle growth, pregnant rats were administered dexamethasone (DEX: 1 mg/L drinking water) from embryonic day (ED) 13 to ED21. Their responses were compared to pair-fed (PF) and ad libitum-fed controls (CON). Bromodeoxyuridine (BrdU) was administered before delivery to measure myonuclear accretion. Fetal hind limb and diaphragm muscles were collected at term and analyzed for myofiber cross-sectional area (CSA), total and BrdU+ myonuclei, Pax7+ nuclei, MyoD and myogenin protein and mRNA abundance and myosin heavy chain (MyHC) isoform composition. Mean fiber CSA, myonuclei/myofiber and Pax7+ nuclei/myofiber ratios were reduced in DEX compared to those in CON and PF muscles; CSA/myonucleus, BrdU+/total myonuclei and BrdU+ myonuclei/Pax7+ nuclei were similar among groups. Myogenin abundance was reduced and MyHC-slow was increased in DEX fetuses. The data are consistent with GLC inhibition of muscle progenitor cell proliferation limiting satellite cell and myonuclear accretion. The response of PF-fed compared to CON muscles indicated that decreased food consumption by DEX dams contributed to the smaller myofiber CSA but did not affect Pax7+ nuclear accretion. Thus, the effect on satellite cell reserve and myonuclear number also contributes to the blunting of fetal muscle growth by GLC.

scholarly journals Integrin signaling: linking mechanical stimulation to skeletal muscle hypertrophy

2019 ◽  
Vol 317 (4) ◽  
pp. C629-C641 ◽  
Author(s):  
Marni D. Boppart ◽  
Ziad S. Mahmassani
Keyword(s):  
Skeletal Muscle ◽  
Mechanical Load ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
Integrin Subunit ◽  
Resistance Exercise Training ◽  
Adhesion Protein ◽  
Subunit Mrna

The α7β1-integrin is a transmembrane adhesion protein that connects laminin in the extracellular matrix (ECM) with actin in skeletal muscle fibers. The α7β1-integrin is highly expressed in skeletal muscle and is concentrated at costameres and myotendious junctions, providing the opportunity to transmit longitudinal and lateral forces across the membrane. Studies have demonstrated that α7-integrin subunit mRNA and protein are upregulated following eccentric contractions as a mechanism to reinforce load-bearing structures and resist injury with repeated bouts of exercise. It has been hypothesized for many years that the integrin can also promote protein turnover in a manner that can promote beneficial adaptations with resistance exercise training, including hypertrophy. This review provides basic information about integrin structure and activation and then explores its potential to serve as a critical mechanosensor and activator of muscle protein synthesis and growth. Overall, the hypothesis is proposed that the α7β1-integrin can contribute to mechanical-load induced skeletal muscle growth via an mammalian target of rapamycin complex 1-independent mechanism.

scholarly journals Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3

2017 ◽  
Vol 313 (3) ◽  
pp. C257-C261 ◽  
Author(s):  
Joaquín Pérez-Schindler ◽  
Mary C. Esparza ◽  
James McKendry ◽  
Leigh Breen ◽  
Andrew Philp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Signal Pathways ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Adaptive Growth ◽  
Stat3 Phosphorylation ◽  
Transcription 3

Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle.

scholarly journals Ribosome biogenesis adaptation in resistance training-induced human skeletal muscle hypertrophy

2015 ◽  
Vol 309 (1) ◽  
pp. E72-E83 ◽  
Author(s):  
Vandre C. Figueiredo ◽  
Marissa K. Caldow ◽  
Vivien Massie ◽  
James F. Markworth ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Ribosome Biogenesis ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
D1 Protein ◽  
Transcriptional Level ◽  
Cross Sectional ◽  
Before And After

Resistance training (RT) has the capacity to increase skeletal muscle mass, which is due in part to transient increases in the rate of muscle protein synthesis during postexercise recovery. The role of ribosome biogenesis in supporting the increased muscle protein synthetic demands is not known. This study examined the effect of both a single acute bout of resistance exercise (RE) and a chronic RT program on the muscle ribosome biogenesis response. Fourteen healthy young men performed a single bout of RE both before and after 8 wk of chronic RT. Muscle cross-sectional area was increased by 6 ± 4.5% in response to 8 wk of RT. Acute RE-induced activation of the ERK and mTOR pathways were similar before and after RT, as assessed by phosphorylation of ERK, MNK1, p70S6K, and S6 ribosomal protein 1 h postexercise. Phosphorylation of TIF-IA was also similarly elevated following both RE sessions. Cyclin D1 protein levels, which appeared to be regulated at the translational rather than transcriptional level, were acutely increased after RE. UBF was the only protein found to be highly phosphorylated at rest after 8 wk of training. Also, muscle levels of the rRNAs, including the precursor 45S and the mature transcripts (28S, 18S, and 5.8S), were increased in response to RT. We propose that ribosome biogenesis is an important yet overlooked event in RE-induced muscle hypertrophy that warrants further investigation.

scholarly journals Does habitual dietary intake influence myofiber hypertrophy in response to resistance training? A cluster analysis

2009 ◽  
Vol 34 (4) ◽  
pp. 632-639 ◽  
Author(s):  
Anna E. Thalacker-Mercer ◽  
John K. Petrella ◽  
Marcas M. Bamman
Keyword(s):  
Cluster Analysis ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Muscle Growth ◽  
Daily Intake ◽  
Dietary Recommendations ◽  
Extrinsic Factors ◽  
Cross Sectional

Although resistance exercise training (RT) is a common intervention to stimulate muscle protein synthesis and increase skeletal muscle mass, the optimal daily protein and total energy intakes sufficient to support RT-mediated muscle growth are as yet unclear. Further, the efficacy of RT varies widely among adults of all ages and whether this is attributable to interindividual differences in nutrition is not known. To determine if self-selected daily intake of macronutrients and specific components of dietary protein and fat are predictive of the magnitude of RT-mediated muscle growth, detailed 4-day dietary records were analyzed on 60 subjects previously clustered (K-means cluster analysis) as non-, modest, and extreme responders (non, n = 16; mod, n = 29; xtr, n = 15), based on the magnitudes of change in vastus lateralis myofiber cross-sectional area following a 16-week, 3-day-per-week, high-intensity RT. Despite the marked contrast between 60% myofiber hypertrophy in xtr and zero growth in non, we found no differences among response clusters in daily intakes of energy (mean ± SEM: non 102 ± 8; mod 111 ± 6; xtr 109 ± 5 kJ·kg–1·day–1), protein (non 0.97 ± 0.08; mod 1.07 ± 0.07; xtr 1.05 ± 0.06 g·kg–1·day–1), carbohydrate (non 3.02 ± 0.24; mod 3.18 ± 0.20; xtr 3.14 ± 0.17 g·kg–1·day–1), and fat (non 0.95 ± 0.09; mod 1.05 ± 0.08; xtr 1.03 ± 0.08 g·kg–1·day–1), which generally met or exceeded dietary recommendations. There were no cluster differences in intakes of branched chain amino acids known to stimulate muscle protein synthesis. Using the novel K-means clustering approach, we conclude from this preliminary study that protein and energy intakes were sufficient to facilitate modest and extreme muscle growth during RT and intrinsic or extrinsic factors other than nutrient ingestion apparently impaired the anabolic response in nonresponders.

scholarly journals Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis

2009 ◽  
Vol 106 (4) ◽  
pp. 1403-1411 ◽  
Author(s):  
Micah J. Drummond ◽  
Mitsunori Miyazaki ◽  
Hans C. Dreyer ◽  
Bart Pennings ◽  
Shaheen Dhanani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Age Groups ◽  
Essential Amino Acids ◽  
Exercise Muscle

Muscle growth is associated with an activation of the mTOR signaling pathway and satellite cell regulators. The purpose of this study was to determine whether 17 selected genes associated with mTOR/muscle protein synthesis and the satellite cells/myogenic program are differentially expressed in young and older human skeletal muscle at rest and in response to a potent anabolic stimulus [resistance exercise + essential amino acid ingestion (RE+EAA)]. Twelve male subjects (6 young, 6 old) completed a bout of heavy resistance exercise. Muscle biopsies were obtained before and at 3 and 6 h post RE+EAA. Subjects ingested leucine-enriched essential amino acids at 1 h postexercise. mRNA expression was determined using qRT-PCR. At rest, hVps34 mRNA was elevated in the older subjects ( P < 0.05) while there was a tendency for levels of myoD, myogenin, and TSC2 mRNA to be higher than young. The anabolic stimulus (RE+EAA) altered mRNAs associated with mTOR regulation. Notably, REDD2 decreased in both age groups ( P < 0.05) but the expression of Rheb mRNA increased only in the young. Finally, cMyc mRNA was elevated ( P < 0.05) in both young and old at 6 h post RE+EAA. Furthermore, RE+EAA also increased expression of several mRNAs associated with satellite function in the young ( P < 0.05), while expression of these mRNAs did not change in the old. We conclude that several anabolic genes in muscle are more responsive in young men post RE+EAA. Our data provide new insights into the regulation of genes important for transcription and translation in young and old human skeletal muscle post RE+EAA.

scholarly journals Investigation of niclosamide as a repurposing agent for skeletal muscle atrophy

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252135
Author(s):  
Hyun-Jun Kim ◽  
Ji-Hyung Lee ◽  
Seon-Wook Kim ◽  
Sang-Hoon Lee ◽  
Da-Woon Jung ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Cancer Metastasis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Atrophy ◽  
Differentiation Markers ◽  
Cross Sectional

Skeletal muscle atrophy is a feature of aging (termed sarcopenia) and various diseases, such as cancer and kidney failure. Effective drug treatment options for muscle atrophy are lacking. The tapeworm medication, niclosamide is being assessed for repurposing to treat numerous diseases, including end-stage cancer metastasis and hepatic steatosis. In this study, we investigated the potential of niclosamide as a repurposing drug for muscle atrophy. In a myotube atrophy model using the glucocorticoid, dexamethasone, niclosamide did not prevent the reduction in myotube diameter or the decreased expression of phosphorylated FOXO3a, which upregulates the ubiquitin-proteasome pathway of muscle catabolism. Treatment of normal myotubes with niclosamide did not activate mTOR, a major regulator of muscle protein synthesis, and increased the expression of atrogin-1, which is induced in catabolic states. Niclosamide treatment also inhibited myogenesis in muscle precursor cells, enhanced the expression of myoblast markers Pax7 and Myf5, and downregulated the expression of differentiation markers MyoD, MyoG and Myh2. In an animal model of muscle atrophy, niclosamide did not improve muscle mass, grip strength or muscle fiber cross-sectional area. Muscle atrophy is also feature of cancer cachexia. IC50 analyses indicated that niclosamide was more cytotoxic for myoblasts than cancer cells. In addition, niclosamide did not suppress the induction of iNOS, a key mediator of atrophy, in an in vitro model of cancer cachexia and did not rescue myotube diameter. Overall, these results suggest that niclosamide may not be a suitable repurposing drug for glucocorticoid-induced skeletal muscle atrophy or cancer cachexia. Nevertheless, niclosamide may be employed as a compound to study mechanisms regulating myogenesis and catabolic pathways in skeletal muscle.

scholarly journals Continuous Feeding Does Not Blunt Satellite Cell Abundance, Myonuclear Accretion, or Lean Growth in a Neonatal Piglet Model of Prematurity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 696-696
Author(s):  
Marko Rudar ◽  
Jane Naberhuis ◽  
Agus Suryawan ◽  
Hanh Nguyen ◽  
Candace Style ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Muscle Growth ◽  
Preterm Neonates ◽  
Proliferating Cells ◽  
Cross Sectional ◽  
Orogastric Tube ◽  
Skeletal Muscle Growth ◽  
Lean Growth

Abstract Objectives Lean growth in preterm neonates is poor and may increase the lifelong risk for adverse health outcomes. Strategies are needed to promote skeletal muscle growth in the postnatal period. Skeletal muscle growth, which accounts for the largest fraction of lean mass accretion, requires the coordinated activation of protein synthesis, satellite cell (SC; muscle stem cell) proliferation, differentiation, and fusion into muscle fibers. The objective of this study was to determine the effect of feeding modality on SC abundance, myonuclear accretion, and lean growth in preterm neonatal pigs. Methods Pigs delivered 10 d preterm by C-section (952 ± 205 g) were fitted with an umbilical artery catheter (later replaced with jugular vein catheter) and an orogastric tube for parenteral and enteral nutrition, respectively. Pigs were assigned to continuous (CONT; n = 14; 7.5 mL/[kg·h]) or intermittent bolus (INT; n = 30; 30 mL/kg every 4 h) feeding for 21 d (210 kcal/kg and 16 g protein/kg per d); pigs were advanced from parenteral to enteral feeding over 6 d. Bromodeoxyuridine (BrdU; 25 mg·kg−1) was administered to pigs every 12 h from days 19 to 20, inclusive, to label proliferating cells. Body composition was measured by DXA on day 21. Satellite cell (Pax7+) abundance, myonuclear accretion, and muscle fiber cross-sectional area (CSA) were quantified in the longissimus dorsi muscle by immunofluorescence. Results Sublaminal Pax7+ SC abundance was similar between CONT and INT groups (60.9 vs. 58.3 ± 6.0 per 1000 fibers). The proportion of sublaminal relative to total Pax7+ SCs was similar between CONT and INT groups (78.8 vs. 78.8 ± 2.2%). The abundance of BrdU + myonuclei, an index of myonuclear accretion, did not differ between CONT and INT groups (26.7 vs. 26.7 ± 3.4 per 1000 fibers). Total myonuclei did not differ between CONT and INT groups (420 vs. 403 ± 16 per 1000 fibers). Muscle fiber CSA did not differ between CONT and INT groups (210 vs. 237 ± 15 µm2). Lean and fat masses were similar between groups. Conclusions Unlike term pigs, CONT feeding does not blunt lean growth in preterm pigs compared to INT feeding. The absence of increased lean growth with INT feeding is consistent with the similar SC abundance, myonuclear accretion, and muscle fiber CSA between feeding modalities. Funding Sources Research was supported by NIH and USDA.

Sign in / Sign up

Export Citation Format

Share Document