Table 3 Summary of previous reports describing the known molecular effects of β-AR agonist-induced hypertrophy in skeletal muscle

Increased expression of skeletal muscle contractile proteins

[30, 39, 40]

No significant changes were observed in contractile proteins at 1 and 4 hours in our Illumina array data. In the previous referenced studies, contractile proteins were only examined following chronic β-AR agonist administration. Increased myosin heavy chain was observed at protein level [39], and may not be present at mRNA level.

Increased mRNA expression of myogenin, a key developmental regulator of functional skeletal muscle

[30]

No significant changes were observed in myogenin at 1 and 4 hours in our Illumina array data. In Spurlock et al. [30], increased myogenin mRNA expression was only observed at 24 hours following β-AR agonist administration. Our earlier timepoints may miss this change.

Increased expression of initiators of protein translation

[30]

Our Illumina array data showed no significant changes in any genes that are known initiators of protein translation. In Spurlock et al. [30], increased expression of mRNA encoding initiators of protein translation were observed mainly at 24 hours following β-AR agonist administration. Our earlier timepoints may miss these changes.

Decreased myofibrilar proteolysis via inhibition of the ATP-ubiquitin-dependent proteolytic system

[8, 10, 11]

We observed the induction of four genes associated with ubiquitin-proteolytic system (Ubg, Ubc, Fbxo34 and Usp2). This is in contrast to the referenced studies that demonstrated inhibition of the ATP-ubiquitin-dependent proteolytic system via chronic β-AR agonist administration on skeletal muscle. The induction we observed may represent a mechanism whereby acute β-AR signaling induces proteolysis for myofibril repair following exercise (which is known to induce β-AR signaling [75]).

Decreased myofibrilar proteolysis via Ca²⁺-dependent or calpain-mediated proteolysis

[12]

Our Illumina array data showed no significant changes in any genes associated with calpain-mediated or other Ca²⁺-dependent proteolytic genes.

Decreased expression of SOCS box protein Asb15, which is a negative regulator of protein synthesis and myoblast differentiation

[43–46]

We did not observe repression (or induction) of Asb15 mRNA in the Illumina array data at either timepoint. In the referenced studies, Asb15 is repressed at 12-24 hours. Our earlier timepoints may miss this expression change, however there is the potential for a transcription factor listed in our study to repress Asb15.

Induction of Igf1 mRNA expression

[30]

We did not observe any induction of Igf1 in the Illumina array data at either timepoint. In Spurlock et al. [30], increased expression of Igf1 was observed mainly at 24 hours post β-AR agonist administration.

Induction of Igf2 mRNA expression

[40, 47]

Igf2 was repressed 2.61 fold, however this was removed due to multiple testing correction. Although this result is not consistent with the referenced previous studies, Igf2 mRNA in these previous studies was only examined after chronic β-AR agonist administration.