scholarly journals Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

2014 ◽  
Vol 221 (2) ◽  
pp. R13-R29 ◽  
Author(s):  
Laura D Brown
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Fiber ◽  
Muscle Growth ◽  
Metabolic Health ◽  
Endocrine Regulation ◽  
Intrauterine Environment ◽  
Skeletal Muscle Growth ◽  
Fiber Number ◽  
Muscle Fiber Number

Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present during the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or ‘catch-up’ postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and the risk of cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts toward improving muscle growth early in life to prevent the development of chronic metabolic diseases later in life.

scholarly journals Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Leonardo Martins ◽  
Camila Congentino Gallo ◽  
Tâmisa Seeko Bandeira Honda ◽  
Patrícia Terra Alves ◽  
Roberta Sessa Stilhano ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Transient Expression ◽  
Muscle Injury ◽  
Plasmid Vector ◽  
M2 Macrophage ◽  
Running Speed ◽  
Gm Csf ◽  
Fiber Number ◽  
Muscle Fiber Number

Abstract Background After traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. The sequence of M1 and M2 macrophage accumulation and the duration of each subtype in the injured area may help to direct the relative extent of fibrogenesis and myogenesis during healing. We hypothesized that increasing the number of M1 macrophages early after traumatic muscle injury would produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing. Methods To test this hypothesis, we transfected skeletal muscle with a plasmid vector to transiently express GM-CSF shortly after injury to drive the polarization of macrophages towards the M1 subset. C57BL/6 mouse tibialis anterior (TA) muscles were injured by contusion and electroporated with uP-mGM, which is a plasmid vector that transiently expresses GM-CSF. Myogenesis, angiogenesis, and fibrosis were evaluated by histology, immunohistochemistry, and RT-qPCR; subpopulations of macrophages by flow cytometry; and muscle functioning by the maximum running speed on the treadmill and the recovery of muscle mass. Results Muscle injury increased the number of local M1-like macrophages and decreased the number of M2-like macrophages on day 4, and uP-mGM treatment enhanced this variation. uP-mGM treatment decreased TGF-β1 protein expression on day 4, and the Sirius Red-positive area decreased from 35.93 ± 15.45% (no treatment) to 2.9% ± 6.5% (p < 0.01) on day 30. uP-mGM electroporation also increased Hgf, Hif1α, and Mtor gene expression; arteriole density; and muscle fiber number during regeneration. The improvement in the quality of the muscle tissue after treatment with uP-mGM affected the increase in the TA muscle mass and the maximum running speed on a treadmill. Conclusion Collectively, our data show that increasing the number of M1-like macrophages immediately after traumatic muscle injury promotes muscle recovery with less fibrosis, and this can be achieved by the transient expression of GM-CSF.

Estimation of skeletal muscle fiber number by mean fiber dry weight

1984 ◽  
Vol 56 (1) ◽  
pp. 244-247
Author(s):  
B. F. Timson ◽  
G. A. Dudenhoeffer
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Biceps Brachii ◽  
Estimation Method ◽  
Dry Weight ◽  
Skeletal Muscle Fiber ◽  
Anterior Latissimus Dorsi ◽  
Fiber Number ◽  
Nitric Acid Digestion ◽  
Muscle Fiber Number

The purpose of this study was to determine whether skeletal muscle fiber number could be accurately estimated by the determination of mean fiber dry weight (MFD) and total muscle dry weight. The muscles studied were the soleus, plantaris, gastrocnemius, extensor digitorum longus, tibialis anterior, and biceps brachii of the rat, the anterior latissimus dorsi of the chicken, and the flexor carpi radialis of the cat. Bundles of fibers were carefully separated from the muscle following nitric acid digestion (ND) and placed in groups of similar length. MFD determined from 400 to 800 fibers from each group was used to estimate the number of fibers in the remainder of the group. Estimated fiber number was compared with the fiber number determined in the muscle from the contralateral limb by the ND method. No difference in fiber number was observed between the ND method and the MFD estimation method for any of the muscles used in the study. The results indicate that the MFD estimation method is an accurate and relatively rapid method of fiber number determination in skeletal muscle.

Abstract 1432: Cardiomyocyte Myostatin Contributes to Skeletal Muscle Wasting in Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Joerg Heineke ◽  
Mannix Auger-Messier ◽  
Michelle Sargent ◽  
Allen York ◽  
Stephen Welle ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Wasting ◽  
Muscle Growth ◽  
Precursor Protein ◽  
Mouse Serum ◽  
Skeletal Muscle Growth ◽  
Skeletal Muscle Wasting

Introduction: Skeletal muscle wasting during heart failure constitutes a major therapeutic challenge. The TGFβ superfamily member myostatin is a negative regulator of skeletal muscle growth. For example, elimination of myostatin (MSTN) in adult mice through an inducible Cre/lox recombination strategy has been shown to increase skeletal muscle mass by about 25%. Previous studies identified skeletal muscle and to a lesser extent cardiac and fat tissue as the source of MSTN production in the body. MSTN is produced as a precursor protein, which has been suggested to constitute the main reservoir of the protein in skeletal muscle. In mouse serum, however, MSTN is abundantly present in its mature form, which consists of the C-terminal fragment of the precursor protein. Results: We detected high levels of the mature MSTN protein (MM) in the mouse myocardium by western blotting. Interestingly, MM was significantly upregulated in the myocardium of mice subjected to long-term myocardial pressure overload (TAC, 12 weeks; protein levels: sham 100±22% vs. TAC 218±18%, p<0.01). In contrast, MM was barely detectable in mouse skeletal muscle. Immunhistochemical staining confirmed enhanced cardiomyocyte MSTN production after TAC. To determine the impact of cardiomyocyte MSTN on skeletal muscle growth during heart failure, we crossed cardiomyocyte specific Nkx2.5-Cre mice with mice in which the MSTN exon3 was flanked by loxp sites to eliminate expression of mature MSTN selectively in cardiomyocytes (CKO mice). While CKO mice did not have significant changes in skeletal muscle mass after a sham operation (e.g. quadriceps, normalized to tibia length: sham control 111±3.8 g/cm vs. sham CKO 106±4.3 g/cm), a 16% increase in skeletal muscle mass was observed in CKO mice after longterm TAC (quadriceps: TAC control 100±3.3 g/cm vs. TAC CKO 116±5.3 g/cm, p<0.05). In line with these results, mice with cardiomyocyte specific overexpression of MSTN (MSTN-Tg) showed a reduction in skeletal muscle mass (quadriceps: control 91±2.5 g/cm vs. MSTN-Tg 82±1.5 g/cm, p<0.05). Conclusion: Myocardial MSTN contributes to the development of skeletal muscle wasting in heart failure, most likely through an endocrine mechanism involving its secretion into the circulatory system.

scholarly journals Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis

1996 ◽  
Vol 81 (4) ◽  
pp. 1584-1588 ◽  
Author(s):  
George Kelley
Keyword(s):  
Skeletal Muscle ◽  
Confidence Interval ◽  
Muscle Fiber ◽  
Meta Analysis ◽  
Compensatory Hypertrophy ◽  
Skeletal Muscle Fiber ◽  
Fiber Number ◽  
Nitric Acid Digestion ◽  
Mechanical Overload ◽  
Muscle Fiber Number

Kelley, George. Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis. J. Appl. Physiol. 81(4): 1584–1588, 1996.—With use of the meta-analytic approach, the purpose of this study was to examine the effects of mechanical overload on skeletal muscle fiber number in animals. A total of 17 studies yielding 37 data points and 360 subjects met the initial inclusion criteria: 1) “basic” research studies published in journals, 2) animals (no humans) as subjects, 3) control group included, 4) some type of mechanical overload (stretch, exercise, or compensatory hypertrophy) used to induce changes in muscle fiber number, and 5) sufficient data to accurately calculate percent changes in muscle fiber number. Across all designs and categories, statistically significant increases were found for muscle fiber number [15.00 ± 19.60% (SD), 95% confidence interval = 8.65–21.53], muscle fiber area (31.60 ± 44.30%, 95% confidence interval = 16.83–46.37), and muscle mass (90.50 ± 86.50%, 95% confidence interval = 61.59–119.34). When partitioned according to the fiber-counting technique, larger increases in muscle fiber number were found by using the histological vs. nitric acid digestion method (histological = 20.70%, nitric acid digestion = 11.10%; P = 0.14). Increases in fiber number partitioned according to species were greatest among those groups that used an avian vs. mammalian model (avian = 20.95%, mammalian = 7.97%; P = 0.07). Stretch overload yielded larger increases in muscle fiber number than did exercise and compensatory hypertrophy (stretch = 20.95%, exercise = 11.59%, compensatory hypertrophy = 5.44%; P = 0.06). No significant differences between changes in fiber number were found when data were partitioned according to type of control (intra-animal = 15.20%, between animal = 13.90%; P = 0.82) or fiber arrangement of muscle (parallel = 15.80%, pennate = 11.60%; P = 0.61). The results of this study suggest that in several animal species certain forms of mechanical overload increase muscle fiber number.

scholarly journals Effects of spaceflight and thyroid deficiency on hindlimb development. I. Muscle mass and IGF-I expression

2000 ◽  
Vol 88 (3) ◽  
pp. 894-903 ◽  
Author(s):  
G. R. Adams ◽  
S. A. McCue ◽  
P. W. Bodell ◽  
M. Zeng ◽  
K. M. Baldwin
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Growth ◽  
Somatic Growth ◽  
The Body ◽  
Neonatal Rats ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I ◽  
The Impact

Thyroid deficiency (TD) in neonatal rats causes reduced growth of skeletal muscle that is disproportionately greater than that for other tissues (G. R. Adams, S. A. McCue, M. Zeng, and K. M. Baldwin. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 276: R954–R961, 1999). TD depresses plasma insulin-like growth factor I (IGF-I) levels, suggesting a mechanism for this effect. We hypothesized that TD and exposure to spaceflight (SF) would interact to reduce skeletal muscle growth via a reduction in IGF-I levels. Neonatal rats were flown in space for 16 days. There was a similar, nonadditive reduction in the growth of the body (∼50%) and muscle weight (fast muscles, ∼60%) with either TD or SF. In the soleus muscle, either SF or TD alone resulted in growth reductions that were augmented by SF-TD interactions. There were strong correlations between 1) muscle mass and muscle IGF-I levels and 2) circulating IGF-I and body weight. These results indicate that either hypothyroidism or exposure to SF will limit the somatic and muscle-specific growth of neonatal rats. The impact of these perturbations on skeletal muscle growth is relatively greater than the effect on somatic growth. The mechanisms by which either TD or SF impact growth appear to have a common pathway involving the control of plasma and muscle IGF-I concentrations.

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.

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