<section style="padding: 0px; margin: 0px; color: rgb(0, 0, 0); font-family: Verdana, Arial, Helvetica, sans-serif; font-size: 11px; line-height: 16px; text-align: left; ">Anabolic effects of β-adrenergic receptor agonists (BA) have been widely studied for potential applications in the prevention of muscle atrophy [1,2] and improvement of the efficiency of muscle growth in production livestock [3-5]. Clenbuterol is a β2-adrenergic receptor agonist that has been shown to have a significant effect on muscle metabolism in a variety of muscle atrophy models, including hind-limb suspension atrophy [6,7], starvation induced atrophy [8], and denervation induced atrophy [9,10]. Additionally, clenbuterol is known to induce a significant repartitioning effect by increasing the growth of skeletal muscle at the expense of fat tissues in most livestock species [3,5]. Although it is known that clenbuterol initiates these effects via activation of the β2-adrenergic receptor [3,5], the downstream mechanisms by which activation of these receptors results in increased muscle growth or decreased muscle atrophy are not clear. To date, the expression and activity of specific genes have been investigated in a variety of models in order to implicate specific pathways with the skeletal muscle response to BA. For example, increased abundance of myofibrillar and structural proteins has been demonstrated and appears to result from increases in both transcription and translation of these genes [11-13]. Additionally, endogenous proteinases including genes of the ubiquitin-proteasome pathway and calcium-dependent proteolytic enzymes have been reported to mediate protein turnover in skeletal muscle after administration of BA [14]. Finally, changes in skeletal muscle expression of IGF1 and IGF2 mRNA have been observed shortly after the administration of clenbuterol to rodents [15], suggesting the regulation of these growth factors may be important in the initial response of skeletal muscle to BA.
Although investigations of candidate genes have been informative in terms of implicating individual pathways in the skeletal muscle response to BA, they have not provided a global view of changes occurring in the tissue, and have been limited to the investigation of genes with known functions. Thus, the objective of the current research was to define changes in the global gene expression profile of skeletal muscle in response to administration of the BA clenbuterol. Two time points relative to clenbuterol administration were investigated in order to compare gene expression profiles following short- (24 hour; 24 h) and long- (10 day; 10 D) term clenbuterol administration in mice. The Affymetrix platform was chosen for the analysis of gene expression in order to investigate the most comprehensive collection of genes available.
</section><section style="padding: 0px; margin: 0px; color: rgb(0, 0, 0); font-family: Verdana, Arial, Helvetica, sans-serif; font-size: 11px; line-height: 16px; text-align: left; ">[h=3]Results[/h][h=4]Clenbuterol stimulated an anabolic response[/h]A significant effect of clenbuterol on blood urea nitrogen (BUN) was observed due to decreased BUN in 24 h compared to control (C) treatment groups (P < 0.01; Figure 1). Although average BUN of 10 D treated mice was less than that of C mice, this difference was not statistically significant (P> 0.05). Body weight gain tended to differ among the three groups of mice (P = 0.06), with a significant increase in body weight gain observed following 10 D clenbuterol administration compared to the C group (P < 0.05; Figure 2).
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Although investigations of candidate genes have been informative in terms of implicating individual pathways in the skeletal muscle response to BA, they have not provided a global view of changes occurring in the tissue, and have been limited to the investigation of genes with known functions. Thus, the objective of the current research was to define changes in the global gene expression profile of skeletal muscle in response to administration of the BA clenbuterol. Two time points relative to clenbuterol administration were investigated in order to compare gene expression profiles following short- (24 hour; 24 h) and long- (10 day; 10 D) term clenbuterol administration in mice. The Affymetrix platform was chosen for the analysis of gene expression in order to investigate the most comprehensive collection of genes available.
</section><section style="padding: 0px; margin: 0px; color: rgb(0, 0, 0); font-family: Verdana, Arial, Helvetica, sans-serif; font-size: 11px; line-height: 16px; text-align: left; ">[h=3]Results[/h][h=4]Clenbuterol stimulated an anabolic response[/h]A significant effect of clenbuterol on blood urea nitrogen (BUN) was observed due to decreased BUN in 24 h compared to control (C) treatment groups (P < 0.01; Figure 1). Although average BUN of 10 D treated mice was less than that of C mice, this difference was not statistically significant (P> 0.05). Body weight gain tended to differ among the three groups of mice (P = 0.06), with a significant increase in body weight gain observed following 10 D clenbuterol administration compared to the C group (P < 0.05; Figure 2).
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