Biology subjects

Shepherd, S. O.

Publications and source records attributed to Shepherd, S. O..

3 recordsLinked to original sources

bioRxiv2025

Increased contact between lipid droplets and mitochondria in skeletal muscles of male elite endurance athletes

Endurance athletes exhibit higher skeletal muscle mitochondrial and lipid droplet (LD) content compared to recreationally active individuals, along with greater whole-body oxygen uptake and maximal fat oxidation rates. In this study, we investigated if these differences manifest in a greater LD-mitochondria contact and how this may relate to the organelles size, shape, and numerical densities. We obtained skeletal muscle biopsies from 17 male elite triathletes and road cyclists and 7 recreationally active men. Using quantitative transmission electron microscopy, we found that the endurance athletes had 2-3-fold greater LD-mitochondria contact length than the recreationally active individuals. This was related to higher numerical densities of both mitochondria and LDs in the intermyofibrillar space. Adding data from untrained individuals with equally high intermyofibrillar LD density as the endurance athletes revealed a 24% greater LD-mitochondria contact length in the endurance athletes. We observed small trivial differences in the shape of both organelles between populations. However, large mitochondrial profiles were more elongated and irregular in shape compared to small mitochondrial profiles, while large LD profiles were more circular and less irregular than small LD profiles. Within the group of athletes, large intermyofibrillar LD profiles correlated with a high fraction of PLIN5-positive LDs and their maximal fat oxidation rate was positively associated with an interaction between the profile size of both intermyofibrillar LDs and mitochondria. In conclusion, male endurance athletes have a greater LD-mitochondria contact than recreationally active and untrained individuals. This muscular phenotype is restricted to the intermyofibrillar space and to fibres rich in mitochondria.

physiology↗

bioRxiv2020

The methylome and comparative transcriptome after high intensity sprint exercise in human skeletal muscle

The methylome and transcriptome signature following exercise that is physiologically and metabolic relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we undertook two different sport/exercise relevant high-intensity sprint running protocols in humans using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) sprint exercise. We took skeletal muscle biopsies from the vastus lateralis 30 minutes and 24 hours post exercise followed by 850K methylation arrays and comparative analysis with recent sprint and acute aerobic exercise meta-analysis transcriptomes. Despite matched intensity (speed x distance and number of accelerations/decelerations) between COD and ST exercise, COD exercise elicited greater movement (GPS Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) loading compared with ST exercise. The exercise response alone across both conditions evoked extensive alterations in the methylome immediately post and 24 hrs after exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST sprint exercise, particularly enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. A finding that was more prominent immediately post exercise. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of the genes altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we discovered that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased mRNA expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PGC1- and NR4A3, 3 hrs post COD vs. ST exercise. Overall, we demonstrate that increased physiological load via change of direction sprint exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise. These data imply that introducing changes in direction into high intensity running protocols could serve as an important modulator of a favourable epigenomic and transcriptomic landscape in response to exercise in athletes and trigger greater skeletal muscle remodelling through enhanced gene expression.

physiology↗

bioRxiv2019

Neuromuscular fatigue and recovery after strenuous exercise depends on skeletal muscle size and stem cell characteristics

Hamstring muscle injury is highly prevalent in sports involving repeated maximal sprinting. Although neuromuscular fatigue is thought to be a risk factor, the mechanisms underlying the fatigue response to repeated maximal sprints are unclear. Here, we show that repeated maximal sprints induce neuromuscular fatigue accompanied with a prolonged strength loss in hamstring muscles. The immediate hamstring strength loss was linked to both central and peripheral fatigue, while prolonged strength loss was associated with indicators of muscle damage. The kinematic changes immediately after sprinting likely protected fatigued hamstrings from excess elongation stress, while larger hamstring muscle physiological cross-sectional area and lower myoblast:fibroblast ratio appeared to protect against fatigue/damage and improve muscle recovery within the first 48 h after sprinting. We have therefore identified novel mechanisms that likely regulate the fatigue/damage response and initial recovery following repeated maximal sprinting in humans.

physiology↗