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Updated: Sep 3, 2025

Quantification of Subcellular Glycogen Distribution in Skeletal Muscle Fibers using Transmission Electron Microscopy
Published on: February 7, 2022
The Role of Muscle Glycogen Content and Localization in High-Intensity Exercise Performance: A Placebo-Controlled
Jeppe F Vigh-Larsen1, Niels Ørtenblad2, Joachim Nielsen2
1Department of Public Health, Aarhus University, Aarhus, DENMARK.
Purpose:
We investigated the coupling between muscle glycogen content and localization and high-intensity exercise performance using a randomized, placebo-controlled, parallel-group design with emphasis on single-fiber subcellular glycogen concentrations and sarcoplasmic reticulum Ca 2+ kinetics.
Methods:
Eighteen well-trained participants performed high-intensity intermittent glycogen-depleting exercise, followed by randomization to a high- (CHO; ~1 g CHO·kg -1 ·h -1 ; n = 9) or low-carbohydrate placebo diet (PLA, <0.1 g CHO·kg -1 ·h -1 ; n = 9) for a 5-h recovery period. At baseline, after exercise, and after the carbohydrate manipulation assessments of repeated sprint ability (5 × 6-s maximal cycling sprints with 24 s of rest), neuromuscular function and ratings of perceived exertion during standardized high-intensity cycling (~90% Wmax ) were performed, while muscle and blood samples were collected.
Results:
The exercise and carbohydrate manipulations led to distinct muscle glycogen concentrations in CHO and PLA at the whole-muscle (291 ± 78 vs 175 ± 100 mmol·kg -1 dry weight (dw), P = 0.020) and subcellular level in each of three local regions ( P = 0.001-0.046). This was coupled with near-depleted glycogen concentrations in single fibers of both main fiber types in PLA, especially in the intramyofibrillar region (within the myofibrils). Furthermore, increased ratings of perceived exertion and impaired repeated sprint ability (~8% loss, P < 0.001) were present in PLA, with the latter correlating moderately to very strongly ( r = 0.47-0.71, P = 0.001-0.049) with whole-muscle glycogen and subcellular glycogen fractions. Finally, sarcoplasmic reticulum Ca 2+ uptake, but not release, was superior in CHO, whereas neuromuscular function, including prolonged low-frequency force depression, was unaffected by dietary manipulation.
Conclusions:
Together, these results support an important role of muscle glycogen availability for high-intensity exercise performance, which may be mediated by reductions in single-fiber levels, particularly in distinct subcellular regions, despite only moderately lowered whole-muscle glycogen concentrations.
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