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.

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

IGF-I/PI3K/Akt and IGF-I/MAPK/ERK pathways in vivo in skeletal muscle are regulated by nutrition and contribute to somatic growth in the fine flounder

2011 ◽  
Vol 300 (6) ◽  
pp. R1532-R1542 ◽  
Author(s):  
Eduardo N. Fuentes ◽  
Björn Thrandur Björnsson ◽  
Juan Antonio Valdés ◽  
Ingibjörg Eir Einarsdottir ◽  
Belen Lorca ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nutritional Status ◽  
Signaling Pathways ◽  
Growth Parameters ◽  
Muscle Growth ◽  
Somatic Growth ◽  
Akt Signaling ◽  
Skeletal Muscle Growth ◽  
Igf I

The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Nutrition also affects skeletal muscle growth, activating intracellular pathways and inducing protein synthesis and accretion. Thus, both hormonal and nutritional signaling regulate muscle mass. In this context, plasma IGF-I levels and the activation of both pathways in response to food were evaluated in the fine flounder using fasting and refeeding trials. The present study describes for the first time in a nonmammalian species that the MAPK/ERK and PI3K/Akt are activated by exogenous circulating IGF-I, as well as showing that the MAPK/ERK pathway activation is modulated by the nutritional status. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. Together, these results suggest that the nutritionally managed IGF-I could be regulating the activation of the MAPK/ERK and the PI3K/Akt signaling pathways differentially according to the nutritional status, triggering different effects in growth parameters and therefore contributing to somatic growth in fish. This study contributes to the understanding of the nutrient regulation of IGF-I and its signaling pathways in skeletal muscle growth in nonmammalian species, therefore providing insight concerning the events controlling somatic growth in vertebrates.

Influence of varying degrees of malnutrition on IGF-I expression in the rat diaphragm

2003 ◽  
Vol 95 (2) ◽  
pp. 555-562 ◽  
Author(s):  
Michael I. Lewis ◽  
Hongyan Li ◽  
Zhi-Shen Huang ◽  
Manmohan S. Biring ◽  
Bojan Cercek ◽  
...  
Keyword(s):  
Muscle Protein ◽  
Muscle Growth ◽  
The Body ◽  
Diaphragm Muscle ◽  
Fiber Types ◽  
Mrna Levels ◽  
Adult Rats ◽  
Cross Sectional ◽  
Igf I ◽  
The Impact

This study evaluated the impact of varying degrees of prolonged malnutrition on the local insulin-like growth factor-I (IGF-I) system in the costal diaphragm muscle. Adult rats were provided with either 60 or 40% of usual food intake over 3 wk. Nutritionally deprived (ND) animals (i.e., ND60 and ND40) were compared with control (Ctl) rats fed ad libitum. Costal diaphragm fiber types and cross-sectional areas were determined histochemically. Costal diaphragm muscle IGF-I mRNA levels were determined by RT-PCR. Serum and muscle IGF-I peptide levels were determined by using a rat-specific radioimmunoassay. The body weights of Ctl rats increased by 5%, whereas those of ND60 and ND40 animals decreased by 16 and 26%, respectively. Diaphragm weights were reduced by 17 and 27% in ND60 and ND40 animals, respectively, compared with Ctl. Diaphragm fiber proportions were unaffected by either ND regimen. Significant atrophy of both type IIa and IIx fibers was noted in the ND60 group, whereas atrophy of all three fiber types was observed in the diaphragm of ND40 rats. Serum IGF-I levels were reduced by 62 and 79% in ND60 and ND40 rats, respectively, compared with Ctl. Diaphragm muscle IGF-I mRNA levels in both ND groups were similar to those noted in Ctl. In contrast, IGF-I concentrations were reduced by 36 and 42% in the diaphragm muscle of ND60 and ND40 groups, respectively, compared with Ctl. We conclude that the local (autocrine/paracrine) muscle IGF-I system is affected in our models of prolonged ND. We propose that this contributes to disordered muscle protein turnover and muscle cachexia with atrophy of muscle fibers. This is particularly so in view of recent data demonstrating the importance of the autocrine/paracrine system in muscle growth and maintenance of fiber size.

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 Role of IGF-I in follistatin-induced skeletal muscle hypertrophy

2015 ◽  
Vol 309 (6) ◽  
pp. E557-E567 ◽  
Author(s):  
Caroline Barbé ◽  
Stéphanie Kalista ◽  
Audrey Loumaye ◽  
Olli Ritvos ◽  
Pascale Lause ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Hypertrophy ◽  
Muscle Growth ◽  
Skeletal Muscle Hypertrophy ◽  
Low Concentrations ◽  
Igf I

Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth.

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.

Modulation of IGF mRNA abundance during stretch-induced skeletal muscle hypertrophy and regression

1994 ◽  
Vol 76 (5) ◽  
pp. 2026-2030 ◽  
Author(s):  
S. M. Czerwinski ◽  
J. M. Martin ◽  
P. J. Bechtel
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Mrna Abundance ◽  
Mrna Levels ◽  
Muscle Weight ◽  
Igf I ◽  
Compensatory Muscle Hypertrophy ◽  
First Time

Increased load on a muscle (synergistic overload or stretch) results in muscle hypertrophy. The expression of insulin-like growth factor I (IGF-I) mRNA in rat skeletal muscle is increased during synergistic overload-induced hypertrophy. Although it has also been established that fasting animals lose muscle protein, it has been shown that compensatory muscle hypertrophy occurs in adult fasting rats that are undergoing a net loss of body weight. The purpose of this investigation was to determine whether a relationship exists between IGF-I mRNA levels and muscle growth and regression. This was accomplished by examining whether IGF-I mRNA levels were altered during muscle hypertrophy after stretch and regression and the effect of fasting on IGF-I mRNA levels during stretch-induced hypertrophy. Patagialis (PAT) muscle weights increased 13 and 44% at 2 and 11 days of stretch, respectively. However, after removal of the stretch stimulus on day 11, PAT weights began to decrease, reaching control weights by 18 days. During the first time point (2 days), PAT muscle IGF-I mRNA remained constant. IGF-I mRNA abundance was threefold greater than contralateral control levels by 11 days of stretch. IGF-I mRNA levels decreased but remained significantly above control levels throughout the regression of hypertrophy (13, 18, and 25 days). Fasting did not alter PAT muscle response to stretch. After 11 days of stretch, PAT muscle weight increased 60% compared with contralateral control muscles and IGF-I mRNA levels increased three-fold. This study supports a role for IGF-I in muscle hypertrophy but not muscle atrophy.

scholarly journals Altered chicken thyroid hormone metabolism with chronic GH enhancement in vivo: consequences for skeletal muscle growth

2000 ◽  
Vol 166 (3) ◽  
pp. 609-620 ◽  
Author(s):  
R Vasilatos-Younken ◽  
Y Zhou ◽  
X Wang ◽  
JP McMurtry ◽  
RW Rosebrough ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Thyroid Hormone ◽  
Muscle Growth ◽  
Somatic Growth ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Igf I ◽  
Dose Dependent

In contrast to most vertebrates, GH reportedly has no effect upon somatic growth of the chicken. However, previous studies employed only one to two dosages of the hormone, and limited evidence exists of a hyperthyroid response that may confound its anabolic potential. This study evaluated the effects of 0, 10, 50, 100 and 200 microgram/kg body weight per day chicken GH (cGH) (0-200 GH) infused i.v. for 7 days in a pulsatile pattern to immature, growing broiler chickens (9-10 birds/dosage). Comprehensive profiles of thyroid hormone metabolism and measures of somatic growth were obtained. Overall (average) body weight gain was reduced 25% by GH, with a curvilinear, dose-dependent decrease in skeletal (breast) muscle mass that was maximal (12%) at 100 GH. This profile mirrored GH dose-dependent decreases in hepatic type III deiodinase (DIII) activity and increases in plasma tri-iodothyronine (T(3)), with bot! h also maximal (74 and 108% respectively) at 100 GH. No effect on type I deiodinase was observed. At the maximally effective dosage, hepatic DIII gene expression was reduced 44% versus controls. Despite dose-dependent, fold-increases in hepatic IGF-I protein content, circulating IGF-I was not altered with GH infusion, suggesting impairment of hepatic IGF-I release. Significant, GH dose-dependent increases in plasma non-esterified fatty acid and glucose, and overall decreases in triacylglycerides were also observed. At 200 GH, feed intake was significantly reduced (19%; P<0.05) versus controls; however, additional control birds pair-fed to this level did not exhibit any responses observed for GH-treated birds. The results of this study support a pathway by which GH impacts on thyroid hormone metabolism beginning at a pretranslational level, with reduced hepatic DIII gene expression, translating to reduced protein (enzyme) ex! pression, and reflected in a reduced level of peripheral T(3)-degrading activity. This contributes to decreased conversion of T(3) to its inactive form, thereby elevating circulating T(3) levels. The hyper-T(3) state leads to reduced net skeletal muscle deposition, and may impair release of GH-enhanced, hepatic IGF-I. In conclusion, GH has significant biological effects in the chicken, but profound metabolic actions predominate that may confound positive, IGF-I-mediated skeletal muscle growth.

scholarly journals PSIX-29 JAK2-STAT3 Pathway Mediated Satellite Cell Apoptosis to Govern Skeletal Muscle Growth with Lysine

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 334-334
Author(s):  
Zhi-wen Song ◽  
Cheng-long Jin ◽  
Mao Ye ◽  
Chun-qi Gao ◽  
Hui-chao Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Longissimus Dorsi ◽  
Control Group ◽  
Stat3 Pathway ◽  
Skeletal Muscle Growth ◽  
Longissimus Dorsi Muscle ◽  
Dorsi Muscle ◽  
Pathway Inhibition ◽  
Induced Apoptosis

Abstract Apoptosis is programmed cell death that can be stimulated by external stress or nutrition restrictions. Lysine (Lys) is an essential amino acid for pig growth, and the relationship between Lys deficiency caused apoptosis and inhibition of skeletal muscle growth remains unknown. The objective of this study was to investigate whether apoptosis could be regulated by Lys supplementation and the potential mechanism. In current work, 30 male Duroc × Landrace × Large weaned piglets were divided randomly into 3 groups: control group (Lys 1.30%), Lys deficiency group (Lys 0.86%), and Lys rescue group (Lys 0.86%, 0-14d; 1.30%,15–28 d). The experiment lasted for 28 days, and on the morning of 29 d, piglets were slaughtered to collect samples. Isobaric tag for relative and absolute quantification (iTRAQ) proteomics analysis of the longissimus dorsi muscle showed that Janus family tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was involved in Lys deficiency-induced apoptosis and inhibited skeletal muscle growth. Meanwhile, western blotting results of the longissimus dorsi muscle demonstrated that Lys deficiency caused apoptosis (P &lt; 0.05) with the JAK2-STAT3 pathway inhibition (P &lt; 0.05). Interestingly, apoptosis was suppressed (P &lt; 0.05), and the JAK2-STAT3 pathway was reactivated (P &lt; 0.05) after Lys re-supplementation in longissimus dorsi muscle. In addition, results of satellite cells (SCs) isolated from the longissimus dorsi muscle of 5-day-old Landrace piglets showed that Lys deficiency-induced apoptosis (P &lt; 0.05) was mediated by the JAK2-STAT3 pathway inhibition (P &lt; 0.05). Moreover, the JAK2-STAT3 pathway was reactivated (P &lt; 0.05) by Lys re-supplementation and suppressed apoptosis in SCs (P &lt; 0.05), and this effect was blocked (P &lt; 0.05) after SCs treated with AG-490 (a specific inhibitor of JAK2). Collectively, Lys inhibited apoptosis in SCs to govern skeletal muscle growth via the JAK2-STAT3 pathway.

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