Fibre Type-Specific Proteomics Reveals Shared and Distinct Skeletal Muscle Adaptations to Resistance Training and...

Skeletal muscle is essential for metabolic health and physical function. While resistance training promotes muscle hypertrophy, alternative therapeutic strategies are needed for individuals unable to engage in physical activity. Because beta₂-adrenergic stimulation induces muscle growth without mechanical load, we assessed muscle fibre type-specific proteomic adaptations to prolonged beta₂-adrenergic stimulation and resistance training to decipher shared and distinct remodelling patterns.

We collected vastus lateralis biopsies from 21 moderately trained young males (mean ± SD, age: 24 ± 3) before and after 4-week whole-body resistance training (three sessions/week) or daily inhalation of beta₂-adrenergic agonist terbutaline (4 mg/day). From each biopsy, we isolated 40 muscle fibres and typified them using myosin-heavy-chain markers. Fibre pools were analysed using LC-MS/MS-based proteomics.

Beta₂-adrenergic stimulation and resistance training both increased peak-power output during bike-ergometer sprinting (+36 W; 95% CI: 11 to 61, p = 0.007 and +27 W; 95% CI: -1 to 56, p = 0.062, respectively) with no between-treatments differences (treatment × time interaction: p = 0.644). Beta₂-adrenergic stimulation regulated 15 and 23 proteins in Type I and Type II fibres, respectively, compared to 101 and 65 with resistance training. There was a remarkable fibre type-dependent response, with ~7% of regulated proteins shared between Type I and Type II fibres with resistance training and ~3% with beta₂-adrenergic stimulation. Both interventions increased abundance of ribosomal proteins, in which resistance training induced a 25% increase in Type I fibres (p < 0.001) but only 3% in Type II (p = 0.374), while beta₂-adrenergic stimulation increased ribosomal proteins in both fibre types (Type I: 6% increase, p = 0.008; Type II: 9% increase, p < 0.001). Mitochondrial electron-transport-chain protein abundances decreased with both interventions: resistance training reduced abundances mainly in Type I fibres (17% decrease, p < 0.001; Type II: 5% decrease, p = 0.147), while beta₂-adrenergic stimulation caused uniform decreases (Type I: 7% decrease, p = 0.018; Type II: 9% decrease, p = 0.001). Resistance training uniquely increased contractile, cytoskeletal and extracellular matrix proteins, which was not mimicked by beta₂-adrenergic stimulation. S100A13 was upregulated across both interventions and fibre types, whereas MUSTN1 was regulated exclusively with resistance training. Knock-down of S100a13 (-52%; p < 0.001) and Mustn1 (-96%; p < 0.001) in C2C12 myotubes impaired myotube formation (fusion index: S100a13: -5%; p = 0.002; Mustn1: -21%; p < 0.001).

Beta₂-adrenergic stimulation induces proteomic adaptations that partially mimic resistance training, particularly in ribosomal proteins. Shared regulation of S100A13 and unique regulation of MUSTN1 with resistance training suggest distinct and complementary roles in regulating muscle growth. These findings indicate that the beta₂-adrenergic receptor is a potential target to counter muscle atrophic conditions, offering a pharmacological approach for individuals unable to engage in resistance training.