Lindqvist, C. B. | bioRxiv Science

bioRxiv2025

Body Fluid Proteomic Landscape of Acute Exercise

Physical activity improves health, yet the molecular mechanisms remain partially understood. This study presents a high-resolution, time-resolved atlas profiling 10,127 proteins across plasma, saliva, and urine from healthy adults post-acute exercise. Exercise regulated over 3,000 proteins, revealing distinct, fluid-specific temporal dynamics. By integrating fluid-specific exercise signatures with tissue and disease atlases, we delineated the contribution of tissues and associations to various diseases. Network analysis across body fluids elucidated coordinated remodeling in the extracellular matrix and immune activation orchestrating exercise-induced networks. Many exercise-responsive plasma proteins were robust across age, sex, and exercise modalities, indicating a conserved systemic signature. Integration with genetic data established exercise-regulated proteins as modulators of metabolic traits and identified over 200 targeted by approved drugs, highlighting their impact on disease-relevant pathways. This comprehensive atlas, available as an open-access resource https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/, advances our molecular insight into exercise adaptations and enables exerkine discovery, biomarker development, and pharmacological exercise-mimetic strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/656705v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@bf3baforg.highwire.dtl.DTLVardef@e79b11org.highwire.dtl.DTLVardef@1757b9borg.highwire.dtl.DTLVardef@5fddc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIExercise induces robust and distinct changes across body fluid proteomes C_LIO_LITissue remodeling and immune activation drive exercise-induced network expansion C_LIO_LI[~]1,000 exercise-regulated plasma proteins are age, exercise mode, or sex-specific C_LIO_LIGenetic inference identifies druggable exerkines that regulate health and disease C_LI

physiology↗

bioRxiv2023

Insulin and Exercise-induced Phosphoproteomics of Human Skeletal Muscle Identify REPS1 as a New Regulator of Muscle Glucose Uptake

Skeletal muscle regulates glucose uptake in response to insulin and exercise which is critical for maintaining metabolic health. We conducted a comprehensive phosphoproteomic analysis of skeletal muscle from healthy people in response to an acute bout of exercise or insulin stimulation by a hyperinsulinemic euglycemic clamp. Our analysis revealed 233 phosphosites regulated by both exercise and insulin of which most phosphosites were regulated in opposite directions. However, 71 phosphosites on 55 proteins displayed regulation in the same direction, indicating a potential convergence of signaling pathways. We identified the vesicle-associated protein, REPS1, to be phosphorylated at Ser709 in response to both insulin and exercise. REPS1 protein level and Ser709 phosphorylation were closely related to insulin-stimulated glucose uptake in skeletal muscle and required for maximal insulin-stimulated glucose uptake. Furthermore, we observed that insulin triggered phosphorylation of REPS1 Ser709 via P90S6 kinase (RSK) and is impaired in mice and humans with insulin resistance. Collectively, REPS1 is a convergence point for insulin and exercise signaling and a promising therapeutic target in insulin resistance.

biochemistry↗