The effect of the anabolic agent, clenbuterol, on overloaded rat skeletal muscle

1987 ◽  
Vol 7 (2) ◽  
pp. 143-149 ◽  
Author(s):  
C. A. Maltin ◽  
M. I. Delday ◽  
S. M. Hay ◽  
F. G. Smith ◽  
G. E. Lobley ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Drug Treatment ◽  
Growth Response ◽  
Muscle Growth ◽  
Young Male ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Anabolic Agent ◽  
Hypertrophic Growth ◽  
Fibre Size

The dietary administration of clenbuterol to young male rats has been shown to produce a muscle specific hypertrophic growth response. This paper demonstrates that the combined effect of drug treatment and hypertrophic stimulus induced by tenotomy produced an additive effect on muscle growth. This effect was demonstrated in terms of both muscle composition (protein and RNA) and fibre size.

scholarly journals Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels

2021 ◽  
Vol 22 (14) ◽  
pp. 7588
Author(s):  
Zoltan Gombos ◽  
Erika Koltai ◽  
Ferenc Torma ◽  
Peter Bakonyi ◽  
Attila Kolonics ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Male Rats ◽  
Cellular Interactions ◽  
Molecular Signaling ◽  
Protein Breakdown ◽  
Rat Skeletal Muscle ◽  
Plantaris Muscle ◽  
Skeletal Muscle Hypertrophy ◽  
Intensive Investigation

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine

1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Hexokinase Ii ◽  
Epinephrine Infusion ◽  
Glut 4 ◽  
Gastrocnemius Muscles

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.

Anaesthetic Agents and Their Effect on Tissue Protein Synthesis in the Rat

1989 ◽  
Vol 77 (6) ◽  
pp. 651-655 ◽  
Author(s):  
S. D. Heys ◽  
A. C. Norton ◽  
C. R. Dundas ◽  
O. Eremin ◽  
K. Ferguson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Young Male ◽  
Male Rats ◽  
Liver Protein ◽  
Arterial Blood Gas ◽  
Anaesthetic Agents ◽  
Arterial Blood ◽  
Tissue Protein Synthesis

1. Rates of protein synthesis were measured, in vivo, in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 μg/kg). Fractional rates of protein synthesis were determined by injecting [3H]phenylalanine (150 μmol/100 g body weight) 2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates 3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant 4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO2 and O2, except in the group treated with 2.2% halothane.

Energetic driving forces are maintained in resting rat skeletal muscle after dietary creatine supplementation

2001 ◽  
Vol 90 (1) ◽  
pp. 62-66 ◽  
Author(s):  
J. McMillen ◽  
C. M. Donovan ◽  
J. I. Messer ◽  
W. T. Willis
Keyword(s):  
Skeletal Muscle ◽  
Free Energy ◽  
Atp Hydrolysis ◽  
Driving Forces ◽  
Fiber Type ◽  
Energy Charge ◽  
Creatine Supplementation ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Energetic State

The total creatine (TCr) pool of skeletal muscle is composed of creatine (Cr) and phosphocreatine (PCr). In resting skeletal muscle, the ratio of PCr to TCr (PCr/TCr; PCr energy charge) is ∼0.6–0.8, depending on the fiber type. PCr/TCr is linked to the cellular free energy of ATP hydrolysis by the Cr kinase equilibrium. Dietary Cr supplementation increases TCr in skeletal muscle. However, many previous studies have reported data indicating that PCr/TCr falls after supplementation, which would suggest that Cr supplementation alters the resting energetic state of myocytes. This study investigated the effect of Cr supplementation on the energy phosphates of resting skeletal muscle. Male rats were fed either rodent chow (control) or chow supplemented with 2% (wt/wt) Cr. After 2 wk on the diet, the gastrocnemius and soleus muscles were freeze clamped and removed from anesthetized animals. Cr supplementation increased TCr, PCr, and Cr levels in the gastrocnemius by 20, 22, and 17%, respectively ( P < 0.05). A numerical 6% higher mean soleus TCr in Cr-supplemented rats was not statistically significant. All other energy phosphate concentrations, free energy of ATP hydrolysis, and PCr/TCr were not different between the two groups in either muscle. We conclude that Cr supplementation simply increased TCr in fast-twitch rat skeletal muscle but did not otherwise alter resting cellular energetic state.

scholarly journals Proteomic profile and morphological characteristics of skeletal muscle from the fast- and slow-growing yellow perch (Perca flavescens)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karolina Kwasek ◽  
Young Min Choi ◽  
Hanping Wang ◽  
Kichoon Lee ◽  
John Mark Reddish ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Yellow Perch ◽  
Glycogen Phosphorylase ◽  
Expression Patterns ◽  
Muscle Growth ◽  
Perca Flavescens ◽  
Morphological Characteristics ◽  
Gene Products ◽  
Hypertrophic Growth ◽  
Slow Growing

AbstractThe objective of the present study was to compare skeletal muscle proteomic profiles, histochemical characteristics, and expression levels of myogenic regulatory factors (MRFs) between fast- versus slow-growing yellow perch Perca flavescens and identify the proteins/peptides that might play a crucial role in the muscle growth dynamic. Yellow perch were nursed in ponds for 6 weeks from larval stage and cultured in two meter diameter tanks thereafter. The fingerlings were graded to select the top 10% and bottom 10% fish which represented fast- and slow-growing groups (31 yellow perch per each group). Our statistical analyses showed 18 proteins that had different staining intensities between fast- and slow-growing yellow perch. From those proteins 10 showed higher expression in slow-growers, and 8 demonstrated higher expression in fast-growers. Fast-growing yellow perch with a greater body weight was influenced by both the muscle fiber hypertrophy and mosaic hyperplasia compared to slow-growing fish. These hyperplastic and hypertrophic growth in fast-grower were associated with not only metabolic enzymes, including creatine kinase, glycogen phosphorylase, and aldolase, but also myoD and myogenin as MRFs. Overall, the results of the present study contribute to the identification of different expression patterns of gene products in fast- and slow-growing fish associated with their muscle growth.

scholarly journals The m6A methyltransferase METTL3 regulates muscle maintenance and growth in mice

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jennifer M. Petrosino ◽  
Scott A. Hinger ◽  
Volha A. Golubeva ◽  
Juan M. Barajas ◽  
Lisa E. Dorn ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Muscle Size ◽  
Hypertrophic Response ◽  
Hypertrophic Growth ◽  
Genome Wide ◽  
Muscle Proteome ◽  
Exogenous Delivery ◽  
Muscle Homeostasis

AbstractSkeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome. Here we report genome-wide analysis of mRNA methyladenosine (m6A) dynamics of skeletal muscle hypertrophic growth following overload-induced stress. We show that increases in METTL3 (the m6A enzyme), and concomitantly m6A, control skeletal muscle size during hypertrophy; exogenous delivery of METTL3 induces skeletal muscle growth, even without external triggers. We also show that METTL3 represses activin type 2 A receptors (ACVR2A) synthesis, blunting activation of anti-hypertrophic signaling. Notably, myofiber-specific conditional genetic deletion of METTL3 caused spontaneous muscle wasting over time and abrogated overload-induced hypertrophy; a phenotype reverted by co-administration of a myostatin inhibitor. These studies identify a previously unrecognized post-transcriptional mechanism promoting the hypertrophic response of skeletal muscle via control of myostatin signaling.

scholarly journals Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle

2010 ◽  
Vol 109 (2) ◽  
pp. 511-520 ◽  
Author(s):  
Natasha Fillmore ◽  
Daniel L. Jacobs ◽  
David B. Mills ◽  
William W. Winder ◽  
Chad R. Hancock
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
High Fat Diet ◽  
Chemical Activation ◽  
Additive Effect ◽  
Male Rats ◽  
Fiber Types ◽  
High Fat ◽  
Rat Skeletal Muscle ◽  
Amp Activated Protein Kinase

Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMP-activated protein kinase (AMPK), calcium, and circulating free fatty acids (FFAs). Chronic treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR), a chemical activator of AMPK, or increasing circulating FFAs with a high-fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high-fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high-fat diet (HF), AICAR injections (AICAR), or a high-fat diet and AICAR injections (HF + AICAR) for 6 wk. At the end of the treatment period, markers of mitochondrial content were examined in white quadriceps, red quadriceps, and soleus muscles, predominantly composed of unique muscle-fiber types. In white quadriceps, there was a cumulative effect of treatments on long-chain acyl-CoA dehydrogenase, cytochrome c, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) protein, as well as on citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity. In contrast, no additive effect was noted in the soleus, and in the red quadriceps only β-HAD activity increased additively. The additive increase of mitochondrial markers observed in the white quadriceps may be explained by a combined effect of two separate mechanisms: high-fat diet-induced posttranscriptional increase in PGC-1α protein and AMPK-mediated increase in PGC-1α protein via a transcriptional mechanism. These data show that chronic chemical activation of AMPK and a high-fat diet have a muscle type specific additive effect on markers of fatty acid oxidation, the citric acid cycle, the electron transport chain, and transcriptional regulation.

scholarly journals The effects of dietary energy restriction on overloaded skeletal muscle in rats

2000 ◽  
Vol 84 (5) ◽  
pp. 697-704 ◽  
Author(s):  
Khalid Almurshed ◽  
Katharine Grunewald
Keyword(s):  
Skeletal Muscle ◽  
Control Diet ◽  
Muscle Growth ◽  
Myosin Heavy Chain Isoforms ◽  
Energy Restriction ◽  
Male Rats ◽  
Nutritional Deficiencies ◽  
Hindlimb Muscles ◽  
Dietary Energy Restriction ◽  
Energy Deprivation

We evaluated the effects of three levels of energy intake, 73 % (CON73), 81 % (CON81) and 100 % (CON100) of the ad libitum intake of the control diet, on skeletal muscle growth induced by functional overload in male rats. Unlike most previous studies which have employed chronic or acute food restriction where all nutrients are reduced in the diet, the present study tested the effects of energy deprivation as a single factor without inducing other nutritional deficiencies. Muscular growth of plantaris and soleus muscles was induced by removal of synergist gastrocnemius muscles in one hindlimb; muscles in the other leg were used as sham-operated intra-animal controls. After 30 d, rats on the energy-restricted CON73 and CON81 diets gained less weight and had smaller livers, kidneys, hearts and fat pads (epididymal, retroperitoneal and omental) than CON100 rats (P<0·05). They also had smaller sham-operated plantaris muscles (CON73 -13 %, CON81 -9 %) containing less total protein (CON73 -14 %; CON81 -10 %) than CON100 rats (P<0·05). However, the same measurements in overloaded plantaris muscles were similar among groups. Soleus muscle mass and protein contents were not significantly affected by energy restriction in our study. Percentage distributions of myosin heavy-chain isoforms (types I, IIa, IIx and IIb) were similar among rats in CON100, CON81 and CON73 groups for both plantaris and soleus muscles. We conclude that the growth reduction of plantaris muscle induced by energy restriction at 73 % and 81 % for 30 d was prevented by functional overload in male rats.

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