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BMC genomics2016; 17; 596; doi: 10.1186/s12864-016-2945-2

Differential expression of skeletal muscle genes following administration of clenbuterol to exercised horses.

Abstract: Clenbuterol, a beta2-adrenergic receptor agonist, is used therapeutically to treat respiratory conditions in the horse. However, by virtue of its mechanism of action it has been suggested that clenbuterol may also have repartitioning affects in horses and as such the potential to affect performance. Clenbuterol decreases the percent fat and increases fat-free mass following high dose administration in combination with intense exercise in horses. In the current study, microarray analysis and real-time PCR were used to study the temporal effects of low and high dose chronic clenbuterol administration on differential gene expression of several skeletal muscle myosin heavy chains, genes involved in lipid metabolism and the β2-adrenergic receptor. The effect of clenbuterol administration on differential gene expression has not been previously reported in the horse, therefore the primary objective of the current study was to describe clenbuterol-induced temporal changes in gene expression following chronic oral administration of clenbuterol at both high and low doses. Steady state clenbuterol concentrations were achieved at approximately 50 h post administration of the first dose for the low dose regimen and at approximately 18-19 days (10 days post administration of 3.2 μg/kg) for the escalating dosing regimen. Following chronic administration of the low dose (0.8 μg/kg BID) of clenbuterol, a total of 114 genes were differentially expressed, however, none of these changes were found to be significant following FDR adjustment of the p-values. A total of 7,093 genes were differentially expressed with 3,623 genes up regulated and 3,470 genes down regulated following chronic high dose administration. Of the genes selected for further study by real-time PCR, down-regulation of genes encoding myosin heavy chains 2 and 7, steroyl CoA desaturase and the β2-adrenergic receptor were noted. For most genes, expression levels returned towards baseline levels following cessation of drug administration. This study showed no evidence of modified gene expression following chronic low dose administration of clenbuterol to horses. However, following chronic administration of high doses of clenbuterol alterations were noted in transcripts encoding various myosin heavy chains, lipid metabolizing enzymes and the β2-adrenergic receptor.
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Publication Date: 2016-08-09 PubMed ID: 27506674PubMed Central: PMC4979108DOI: 10.1186/s12864-016-2945-2Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research studied the effects of chronic clenbuterol administration on gene expression in horses, particularly in relation to skeletal muscle myosin heavy chains, lipid metabolism, and the β2-adrenergic receptor. It found that while low doses of clenbuterol did not significantly alter gene expression, higher dosages resulted in changes to numerous genes.

Study Overview

  • The study focused on the effects of clenbuterol, a beta2-adrenergic receptor agonist used to treat respiratory conditions in horses, which is also theorized to have performance-enhancing effects.
  • The investigators specifically studied its effects on muscle genes, with a particular focus on several skeletal muscle myosin heavy chains, genes involved in lipid metabolism, and the β2-adrenergic receptor.
  • Gene expressions were followed using microarray analysis and real-time PCR, tracing both low and high repeated clenbuterol administration over time.

Methodology and Findings

  • Steady-state clenbuterol concentrations were observed approximately 50 hours after the first dose for the low dose regimen, and at around 18-19 days for an escalating dosage program.
  • After chronic administration of a low dose (0.8 μg/kg BID) of clenbuterol, the study noted differential expression in 114 genes but none were found to be significant after adjusting for false discovery rate (FDR).
  • Following other chronic high dose administrations, 3,623 genes were up regulated and 3,470 were down regulated of 7,093 genes differentially expressed.
  • Certain genes were selected for further study through real-time PCR including myosin heavy chains 2 and 7, steroyl CoA desaturase and the β2-adrenergic receptor, which were noted to be down-regulated.
  • For most genes, expression levels went back towards baseline levels following the cessation of drug administration.

Conclusions

  • The study found no evidence of a change in gene expression following chronic low dose administration of clenbuterol.
  • However, chronic high dose administration of the drug did result in alterations to transcripts encoding various myosin heavy chains, lipid metabolizing enzymes and β2-adrenergic receptor.
  • These findings could mean that clenbuterol at high doses has the potential to alter muscle composition and metabolism, and possibly affect performance in horses.

Cite This Article

APA
Knych HK, Harrison LM, Steinmetz SJ, Chouicha N, Kass PH. (2016). Differential expression of skeletal muscle genes following administration of clenbuterol to exercised horses. BMC Genomics, 17, 596. https://doi.org/10.1186/s12864-016-2945-2

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 17
Pages: 596
PII: 596

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA. hkknych@ucdavis.edu.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA. hkknych@ucdavis.edu.
Harrison, Linda M
  • Willow Oak Equine, Woodland, CA, USA.
Steinmetz, Stacy J
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
Chouicha, Nadira
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
Kass, Phil H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA.

MeSH Terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Clenbuterol / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Horses
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Organ Specificity / genetics
  • Transcriptome

Grant Funding

  • P30 CA093373 / NCI NIH HHS

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Citations

This article has been cited 3 times.
  1. Ropka-Molik K, Stefaniuk-Szmukier M, Piórkowska K, Szmatoła T, Bugno-Poniewierska M. Molecular characterization of the apoptosis-related SH3RF1 and SH3RF2 genes and their association with exercise performance in Arabian horses. BMC Vet Res 2018 Aug 14;14(1):237.
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  2. Austin MMP, Ivey JLZ, Shepherd EA, Myer PR. Methodologies to Identify Metabolic Pathway Differences Between Emaciated and Moderately Conditioned Horses: A Review of Multiple Gene Expression Techniques. Animals (Basel) 2025 Oct 10;15(20).
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