Biology subjects

Hawley, J. A.

Publications and source records attributed to Hawley, J. A..

3 recordsLinked to original sources

bioRxiv2026

Subcellular proteomic profiling of human skeletal muscle reveals exercise-induced coordinated and compartment-specific protein remodeling

Exercise training induces extensive protein modifications in skeletal muscle, yet how acute exercise and training-induced molecular responses are spatially coordinated across muscle subcellular compartments remains unclear. Using subcellular fractionation combined with data-independent acquisition mass spectrometry, we profiled skeletal muscle mitochondrial, nuclear, and cytosolic proteomes in response to an acute bout of intense cycling (pre-, mid-, post- and 3 h post-exercise) and after eight weeks of endurance training in 40 healthy adults (20 males and 20 females). Acute exercise triggered coordinated, compartment-specific proteomic remodelling, including reductions in protein translation and import machinery concomitant with increased redox-related proteins. Notably, acute exercise increased markers of ribosomal translation within the mitochondrial fraction, revealing ribosomal scaffold protein RACK1 as a potential regulator of subcellular translational control under contractile stress (confirmed by targeted immunoblotting). The nuclear proteome displayed transient remodelling of RNA-processing and chromatin-associated proteins, while cytosolic changes were modest. Endurance training induced robust proteomic remodelling across all compartments, including increased markers of mitochondrial oxidative metabolism and proteostasis. While there were sex differences at baseline, subcellular proteomic responses were largely conserved between sexes. We provide the first comprehensive, time-course subcellular characterisation of the skeletal muscle proteome, revealing regulation of translational machinery underlying the acute exercise response.

physiology↗

bioRxiv2026

Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway

Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response1-3. Using untargeted metabolomics, here we show that circulating levels of the metabolite para-tyramine-O-sulfate (pTOS) are increased >1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulfation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.

physiology↗

bioRxiv2025

Exercise induces time-dependent but not sex-specific transcriptomic changes in healthy human skeletal muscle

Elucidating the time-dependent transcriptional response of skeletal muscle to exercise is essential for uncovering the molecular mechanisms that drive its health-promoting effects. However, previous studies have been limited by a small number of muscle biopsies, often collected at arbitrary time points post-exercise, and in predominantly male subjects. Using the most comprehensive skeletal muscle biopsy time course following a single session of exercise in both males and females, we identified over 16,600 differentially expressed genes (DEGs), including more than 7,000 novel exercise-responsive genes. Of these DEGs, the magnitude of differential expression in 60% of genes was influenced by cardiorespiratory fitness. Although most mitochondrial genes were differentially expressed after exercise, the majority were downregulated at 24-48 hours, suggesting that mitochondrial protein expression may be regulated by post-transcriptional regulation. Despite 1,193 genes showing sex-specific expression at baseline, exercise-induced gene expression differences were minimal between males and females, suggesting that when cardiorespiratory fitness and exercise stimulus are matched, skeletal muscle adaptations are similar between sexes. To enhance data accessibility, we created an interactive Shiny app (https://BishopLab.shinyapps.io/EXERgene/) that allows users to investigate specific genes and interrogate potential mechanisms of skeletal muscle adaptation to exercise.

physiology↗