The muscle proteome reflects changes in mitochondrial function, cellular stress and proteolysis after 14 days of unilateral lower limb immobilization in active young men.
Level 3 - non-randomized controlled study
Prospective non-randomized repeated-measures physiological intervention study
PubMed 36048851 · doi:10.1371/journal.pone.0273925
What was done
Eighteen healthy young men (mean age 25.4 ± 5.5 years, weight 81.2 ± 11.6 kg) underwent 14 days of unilateral knee-brace immobilization following a 4-week exercise standardization protocol and dietary control. Muscle phenotype (vastus group cross-sectional area, lean mass, unilateral 3-repetition maximum leg press, and VO2max) was measured before and after immobilization. Muscle biopsies were obtained from the vastus lateralis at baseline, day 3, and day 14 to quantify proteomic shifts using SWATH-MS and gene-set enrichment analysis (GSEA).
What was found
Fourteen days of immobilization significantly decreased vastus group cross-sectional area (-9.6 ± 4.6%, P < 0.0001), immobilized leg lean mass (-3.3 ± 3.9%, P = 0.002), unilateral 3-repetition maximum leg press strength (-15.6 ± 9.2%, P < 0.0001), and maximal oxygen uptake (-2.9 ± 5.2%, P = 0.044). SWATH-MS identified 2,281 proteins. Compared to baseline, 2 proteins were differentially expressed at day 3 and 99 proteins at day 14 (FDR < 0.05). At day 14, 322 biological processes were significantly altered (FDR < 0.05, P < 0.001); 77% were positively enriched (linked to cellular stress, targeted proteolysis, and protein-DNA complex modifications), while mitochondrial organization and energy metabolism processes were negatively enriched.
Why it matters
This study provides an unbiased human proteomic profile of disuse muscle atrophy, revealing that 2 weeks of limb immobilization suppresses mitochondrial energy systems while activating cellular stress and targeted proteolysis pathways.
Limits
The study is limited by a small sample size (n = 18) restricted to young, healthy males, limiting generalizability to females, older adults, or clinical populations. There was no parallel non-immobilized control group, and functional validation of the identified hub proteins was not performed.
Cited by
- supports As little as two weeks of leg immobilization can result in nearly a 15 percent loss in quadriceps muscle cross-sectional area.