Dataset Information

Organism-wide secretome mapping of tissue crosstalk in exercise

ABSTRACT: Physical activity is a powerful physiologic stimulus that provides benefits to multiple organ systems and confers protection against disease. These physiologic effects are in part mediated by blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. To globally understand how physical activity reshapes cellular secretomes, here we applied a proximity biotinylation approach to profile cell type-specific secretomes from blood plasma following treadmill running in mice. This organism-wide, 21-cell type, 10-tissue in-vivo secretome atlas reveals complex cell type-specific and bidirectional modulation of secreted proteins across all cell types following exercise training. We identify a gradient of secretome responses across cell types, with secretomes from Pdgfra+ being one of the most exercise-responsive in the entire dataset. Peptide-level correlation analysis revealed widespread and cell type-specific exercise regulation of secreted proteoforms. Finally, we show that exercise-inducible secretion of soluble CES2 proteins from the liver suppresses obesity in high fat diet-fed mouse models. Together, these data identify specific exercise-regulated cell types and secreted proteins and illuminate the dynamic remodeling of cell and tissue crosstalk by physical activity.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Nicholas Riley

LAB HEAD: Jonathan Long

PROVIDER: PXD034535 | Pride | 2023-07-21

REPOSITORIES: Pride

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Publications

Organism-wide, cell-type-specific secretome mapping of exercise training in mice.

Wei Wei W Riley Nicholas M NM Lyu Xuchao X Shen Xiaotao X Guo Jing J Raun Steffen H SH Zhao Meng M Moya-Garzon Maria Dolores MD Basu Himanish H Sheng-Hwa Tung Alan A Li Veronica L VL Huang Wentao W Wiggenhorn Amanda L AL Svensson Katrin J KJ Snyder Michael P MP Bertozzi Carolyn R CR Long Jonathan Z JZ

Cell metabolism 20230503 7

There is a significant interest in identifying blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. Although past studies have focused on an individual molecule or cell type, the organism-wide secretome response to physical activity has not been evaluated. Here, we use a cell-type-specific proteomic approach to generate a 21-cell-type, 10-tissue map of exercise training-regulated secretomes in mice. Our dataset identifies >200 exercise train ...[more]

PMID: 37141889

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Project description:Full title: Eccentric exercise activates novel transcriptional regulation of hypertrophic signaling pathways not affected by hormone changes. Unaccustomed eccentric exercise damages muscle tissue stimulating mechanisms of recovery and remodeling that may be affected by cellular protection by the sex hormone 17β-estradiol (E2). Using cDNA microarrays, we screened for differences in mRNA expression caused by E2 and eccentric exercise. After randomly assignment to 8 days of either placebo (CON) or E2 (EXP), eighteen men performed 150 single-leg eccentric contractions. Muscle biopsies were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after exercise. Serum E2 concentrations increased significantly with supplementation (P < 0.001) but did not affect microarray results. Exercise led to early transcriptional changes in striated muscle activator of Rho signaling (STARS), Rho family GTPase 3 (RND3), mitogen activated protein kinase (MAPK) regulation and the downstream transcription factor FOS. Targeted RT-PCR analysis identified concurrent induction of negative regulators of calcineurin signaling RCAN (P < 0.001) and HMOX1 (P = 0.009). Protein contents were elevated for RND3 at 3H (P = 0.02) and FOS at 48H (P < 0.05). These findings indicate that early RhoA and NFAT signaling and regulation are altered following exercise for muscle remodeling and repair, but are not affected by E2. Eighteen young healthy men volunteered as participants in this study. All subjects were pre-screened to ensure that they were healthy, fit and had not regularly participated in resistance exercise in the preceding 6 months. Body composition was measured using dual energy x-ray absorptiometry (DEXA) scans (Hologic QDR 1000W, Waltham, MA). Thigh muscle cross-sectional area was calculated using anthropomorphic measurements of mid-thigh circumference and skinfold thickness. The subject demographics were (mean ± SD): age, 21 ± 2 y; height, 181 ± 5 cm; weight, 76.9 ± 12.8 kg. Subjects were assigned in a randomized, double-blind manner to either a control (CON, N=9) or experimental (EXP, N=9) group. CON subjects consumed 400 mg glucose polymer (Polycose; Abbott Laboratories, Ross Division, St. Laurent, Quebec, Canada) for 10 days. EXP subjects consumed ~300 mg glucose with 1 mg E2 (Estrace; Shire BioChem, Inc., St. Laurent, Quebec, Canada) for 2 days followed by 2 mg E2 for 8 days. On the morning of the ninth day, subjects reported to the laboratory and performed the exercise protocol. Supplementation continued until the day of the final biopsy and blood collection to maintain serum E2 concentrations throughout the collection protocol. Subjects in both groups were instructed to take one pill at the same time each day and return any unused pills. On the testing day, following a short warm-up (10 min of light cycling), subjects were seated in a Biodex isokinetic dynamometer (System 3, Biodex Medical Systems Inc., Ronkonkoma, NY) with their right leg strapped to a lever arm. The lever arm was programmed to extend their leg to 150º of flexion (where 180º is full extension) at a moderate speed (30º/s), then flex their leg to 90°of flexion at a faster speed (120°/s). During the flexion phase, subjects were instructed to attempt to maximally resist flexion of the knee (i.e. voluntary ‘maximal’ contraction) against the descending lever arm throughout the entire range of motion. The complete test consisted of 15 sets of 10 repetitions, each set separated by 1 minute of rest. Prior to each tissue collection, subjects abstained from any other form of physical exertion (within 72 h), avoided alcohol (within 48 h), ate their habitual diet (within 48 h), and abstained from caffeine (within 12 h). Each subject consumed a 350 Kcal defined formula diet (57% carbohydrates, 15% protein and 28% fat) two hours before each muscle biopsy and did not eat again until after the final biopsy of each session was taken. Muscle biopsies were taken from the vastus lateralis of the control (left) leg during the familiarization session (baseline, BL) and after 8 days of supplementation (post supplementation, PS) and the exercised (right) leg 3 hours (3H) and 48 hours (48H) after exercise, in anatomically distinct sites approximately 6 cm apart. Blood was drawn from the antecubital vein at the same collection times. Muscle and blood samples were processed and stored for future measurements.

Dataset Information

Organism-wide secretome mapping of tissue crosstalk in exercise

Publications

Organism-wide, cell-type-specific secretome mapping of exercise training in mice.

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