Fibre Type–Specific Proteomics Reveals Shared and Distinct Skeletal Muscle Adaptations to Resistance Training and Beta2-Adrenergic Agonist

IF 9.1 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2026-01-25 DOI:10.1002/jcsm.70175

Søren Jessen, Andrea Di Credico, Roger Moreno-Justicia, Lukas Moesgaard, Anders Lemminger, Ben Stocks, Angela Di Baldassarre, Jens Bangsbo, Atul S. Deshmukh, Morten Hostrup

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引用次数: 0

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Abstract Image

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纤维类型特异性蛋白质组学揭示了骨骼肌对阻力训练和β 2-肾上腺素能激动剂的共同和独特的适应性。

骨骼肌对代谢健康和身体功能至关重要。虽然阻力训练促进肌肉肥大，但对于无法从事体育活动的个体，需要其他治疗策略。由于β -肾上腺素能刺激在没有机械负荷的情况下诱导肌肉生长，我们评估了肌肉纤维类型特异性蛋白质组学对长时间β -肾上腺素能刺激和阻力训练的适应，以解读共享的和不同的重塑模式。方法我们收集了21名中等训练年轻男性（平均±SD，年龄：24±3）在4周全身阻力训练（3次/周）或每日吸入β -肾上腺素受体激动剂特布他林（4mg /天）前后的股外侧肌活检。从每次活检中，我们分离出40个肌纤维，并使用肌球蛋白重链标记对其进行分型。纤维池采用LC-MS/MS-based蛋白质组学进行分析。结果β -肾上腺素能刺激和阻力训练均能增加自行车-计力器冲刺时的峰值功率输出（+36 W; 95% CI: 11 ~ 61, p = 0.007和+27 W； 95% CI: -1 ~ 56, p = 0.062），两组间无差异（治疗×时间交互作用：p = 0.644）。β -肾上腺素能刺激分别调节了15种和23种I型和II型纤维中的蛋白质，而阻力训练分别调节了101种和65种。有显著的纤维类型依赖性反应，抗阻训练时约7%的调节蛋白在I型和II型纤维之间共享，β -肾上腺素能刺激时约3%。两种干预措施都增加了核糖体蛋白的丰度，其中阻力训练诱导I型纤维增加25% (p < 0.001)，而II型纤维仅增加3% (p = 0.374)，而β -肾上腺素能刺激增加了两种纤维类型的核糖体蛋白（I型：增加6%，p = 0.008； II型：增加9%，p < 0.001）。两种干预措施均降低了线粒体电子传递链蛋白的丰度：抗阻训练主要降低I型纤维的丰度（降低17%，p < 0.001； II型：降低5%，p = 0.147），而β -肾上腺素能刺激引起均匀降低（I型：降低7%，p = 0.018； II型：降低9%，p = 0.001）。抗阻训练独特地增加了收缩蛋白、细胞骨架蛋白和细胞外基质蛋白，这是β -肾上腺素能刺激无法模仿的。S100A13在干预和纤维类型中均上调，而MUSTN1仅在阻力训练中上调。C2C12肌管中S100a13 （-52%, p < 0.001）和Mustn1 （-96%, p < 0.001）的敲低会损害肌管的形成（融合指数：S100a13: -5%， p = 0.002; Mustn1: -21%, p < 0.001）。结论β -肾上腺素能刺激可诱导部分模拟抗阻训练的蛋白质组适应，尤其是核糖体蛋白。S100A13的共同调控和MUSTN1在抗阻训练中的独特调控表明，它们在调节肌肉生长中具有不同的互补作用。这些发现表明β -肾上腺素能受体是对抗肌肉萎缩的潜在靶点，为无法进行抗阻训练的个体提供了一种药理学方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.