Exercise induces tissue-specific adaptations to enhance cardiometabolic health

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(2), P. 278 - 300

Published: Jan. 5, 2024

The risk associated with multiple cancers, cardiovascular disease, diabetes, and all-cause mortality is decreased in individuals who meet the current recommendations for physical activity. Therefore, regular exercise remains a cornerstone prevention treatment of non-communicable diseases. An acute bout results coordinated interaction between tissues to increased energy demand exercise. Over time, metabolic stress each individual provides basis long-term adaptations across tissues, including system, skeletal muscle, adipose tissue, liver, pancreas, gut, brain. plethora benefits throughout whole body, improved cardiorespiratory fitness, function, glycemic control. Overall, we summarize exercise-induced that occur within how they converge ultimately improve cardiometabolic health.

Language: Английский

---

Molecular insights of exercise therapy in disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 29, 2024

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for prevention and treatment various diseases, underlying biological mechanisms have not been fully elucidated. Several attributed to signaling molecules that are released in response by different tissues such as skeletal muscle, cardiac adipose, liver tissue. These molecules, which collectively termed exerkines, form a heterogenous group bioactive substances, mediating inter-organ crosstalk well structural functional tissue adaption. Numerous scientific endeavors focused on identifying characterizing new mediators with properties. Additionally, some investigations molecular targets exerkines cellular cascades trigger adaption processes. A detailed understanding tissue-specific downstream effects is crucial harness health-related mediated improve targeted programs health disease. Herein, we review current vivo exerkine-induced signal transduction across multiple target highlight preventive therapeutic value exerkine diseases. By aspects research, provide comprehensive overview (i) underpinnings secretion, (ii) receptor-dependent receptor-independent adaption, (iii) clinical implications these disease treatment.

Language: Английский

---

Plasma Proteomic Kinetics in Response to Acute Exercise

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(8), P. 100601 - 100601

Published: June 20, 2023

Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout exercise. Limited data exist regarding kinetic responses plasma proteins and after acute Proteomic profiling 4163 was performed using a large-scale, affinity-based platform 75 middle-aged adults who were referred for treadmill stress testing. Plasma quantified at baseline, peak exercise, 1-h postexercise, those with significant changes both timepoints further examined their associations cardiometabolic traits change aerobic training Health, Risk Factors, Exercise Training Genetics Family Study, 20-week intervention study. A total 765 changed (false discovery rate < 0.05) compared to 128 postexercise. The 56 that included midkine, brain-derived neurotrophic factor, metalloproteinase inhibitor 4, coiled-coil domain-containing protein 126 enriched secreted proteins. majority had concordant direction timepoints. Across all assayed, gene set enrichment analysis showed increased abundance coagulation-related Forty-five associated least one measure adiposity, lipids, glucose homeostasis, or cardiorespiratory fitness 20 training. We identified hundreds novel most resolved 1 h into recovery. Proteins sustained recovery particular interest as biomarkers pathways investigation diseases. These will contribute biochemical roadmap publicly available entire scientific community.

Language: Английский

---

Exercise, exerkines, and cardiometabolic health: from individual players to a team sport

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(11)

Published: May 31, 2023

Exercise confers numerous salutary effects that extend beyond individual organ systems to provide systemic health benefits. Here, we discuss the role of exercise in cardiovascular health. We summarize major findings from human studies cardiometabolic disease. next describe our current understanding cardiac-specific substrate metabolism occurs with acute and response training. subsequently focus on exercise-stimulated circulating biochemicals ("exerkines") as a paradigm for global circuitry exercise, important concepts this emerging field before highlighting exerkines relevant Finally, Review identifies gaps remain science opportunities exist translate biologic insights into improvement.

Language: Английский

---

Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(6), P. 1711 - 1721

Published: June 1, 2024

Abstract Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in feasibility reproducibility CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to 14,145 individuals across four international cohorts with diverse ascertainment methods establish, validate characterize a score. In cohort around 22,000 UK Biobank, score was associated reduced risk all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48–0.52) per 1 s.d. increase). The also multisystem disease provided reclassification discrimination beyond factors, as well modulating high polygenic certain diseases. Finally, observed dynamicity who undertook 20-week exercise training program an association degree effect CRF, suggesting potential personalization recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts are additive genetic risk, potentially modifiable clinically translatable.

Language: Английский

---

Metabolomic and Proteomic Profiling of Athletes Performing Physical Activity under Hypoxic Conditions

Sports, Journal Year: 2024, Volume and Issue: 12(3), P. 72 - 72

Published: March 5, 2024

Proteomic and metabolomic research enables quantitation of the molecular profile athletes. Multiomic profiling was conducted using plasma samples collected from 18 male athletes performing aerobic activity (running) at high altitude. Metabolomic detected changes in levels 4-hydroxyproline, methionine, oxaloacetate, tyrosine during recovery period. Furthermore, proteomic revealed expression proteins contributing to function immune system, muscle damage, metabolic fitness performance, as well hemostasis. Further should focus on developing models monitor training intensity athlete adaptation.

Language: Английский

---

Plasma Proteomic Signatures of Physical Activity Provide Insights into Biological Impacts of Physical Activity and its Protective Role Against Dementia.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Physical activity (PA), including sedentary behavior, is associated with many diseases, Alzheimer's disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against are not entirely understood. To address this knowledge gap, we first assessed conventional observational associations of three self-reported device-based measures circulating levels 2,911 plasma proteins measured in UK Biobank (n max =39,160) functional enrichment identified proteins. We then used bi-directional Mendelian randomization (MR) to further evaluate evidence for causal relationships protein levels. Finally, performed mediation analyses identify that may mediate relationship incident Our findings revealed 41 consistently all 1,027 at least one measure. Both MR study designs converged on appear increase as a result PA, integrin such ITGAV ITGAM, well MXRA8, CLEC4A, CLEC4M, GFRA1, ADGRG2; decrease LEP, LPL, INHBC, CLMP, PTGDS, ADM, OGN, PI3. Functional several relevant processes, cell-matrix adhesion, integrin-mediated signaling, collagen binding. proteins, GDF15, ITGAV, HPGDS, BCAN, MENT, were found dementia, implicating processes synaptic plasticity, neurogenesis inflammation, results provide insights into how affect protect from avenues future research health-promoting effects PA.

Language: Английский

---

Plasma Extracellular Vesicles Biomarkers Linked to Lower Muscle Mass, Function and Physical Performance in Sarcopenia

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2025, Volume and Issue: 16(2)

Published: March 31, 2025

ABSTRACT Background As society ages, identifying individuals at risk of sarcopenia becomes essential. Several plasma biomarkers are used to assess musculoskeletal status, but their results inconsistent. Extracellular vesicles (EVs) investigated as disease due role in transporting molecules and influencing cellular processes. This study the correlation known biomarkers—adiponectin, myostatin, P3NP, CRP TNF‐α—measured from plasma‐derived EVs with muscle mass, function performance an Osteoporosis Sarcopenia cohort Seoul National University Bundang Hospital. Methods Muscle mass was evaluated by measuring appendicular skeletal (ASM) using dual X‐ray absorptiometry calculated ASM/height 2 . Hand grip strength measured a hydraulic hand dynamometer for physical based on Short Physical Performance Battery (SPPB), walking speed five‐time‐sit‐to‐stand test. Density gradient ultracentrifugation isolate plasma, followed confirming expression biomarkers. Multivariate regression analysis, adjusted sex, age, body index, smoking, drinking, bone density, performed. Results The mean age participants 74.3 ± 12.1 years (range, 52.0–96.0), 88.2% being female. Plasma‐derived EV levels myostatin P3NP were significantly associated ( ꞵ = −0.309, p 0.014) SPPB −0.276, 0.029), respectively. TNF‐α strongly correlated −0.313, 0.013). Using receiver‐operating characteristic curve cutoff values three factors determined, allowing be categorized into high low groups. Low group had higher (19.63 kg vs. 17.14 kg, 0.027) faster test times (17.34 s 23.72 s, 0.032). showed stronger (19.87 16.81 0.008), better scores (9.10 8.03, 0.006) (18.31 21.87 0.002). linked speeds (0.82 m/s 0.64 m/s, 0.009) lower SARC‐F (1.73 3.26, 0.029). Conclusion Our research confirmed that EVs‐derived performance. Significant differences these between groups biomarker cutoffs emphasize diagnostic relevance sarcopenia. These findings offer promising avenue effective markers future clinical applications.

Language: Английский

---

Human Plasma Proteomics Links Modifiable Lifestyle Exposome to Disease Risk

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Environmental exposures influence disease risk, yet their underlying biological mechanisms remain poorly understood. We present the Human Exposomic Architecture of Proteome (HEAP), a framework and resource integrating genetic, exposomic, proteomic data to uncover how lifestyle influences through plasma proteins. Applying HEAP 2,686 proteins in 53,014 UK Biobank participants, we identified over 11,000 exposure-protein associations across 135 exposures. Exposures explained substantial portion variation, with 9% more influenced by than genetics. Mediation analyses 270 diseases revealed linking risk; for instance, IGFBP1 IGFBP2 mediated effects exercise diet on type 2 diabetes. These findings were supported concordant shifts interventional studies GLP1 agonists, underscoring therapeutic relevance. provides advancing prevention precision medicine revealing which shapes human health.

Language: Английский

---

Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 5, 2024

Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding precise molecular mechanisms underlying these effects remains incomplete good biomarkers to objectively assess physical are lacking. We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks a combined strength endurance exercise intervention. estimated insulin sensitivity hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, used MRI/MRS evaluate body composition organ fat depots. Muscle subcutaneous adipose tissue biopsies were for mRNA sequencing. Additional association analyses performed samples from up 47,747 individuals UK Biobank, as well using two-sample Mendelian randomization mice models. Following intervention, we observed significant changes 283 proteins. Notably, 66 elevated overweight men positively liver before regimen, but normalized after exercise. Furthermore, 19.7 12.1% exercise-responsive proteins, corresponding expression levels fat, respectively, shown. The protein CD300LG displayed consistent alterations blood, muscle, fat. Serum exhibited positive associations sensitivity, angiogenesis-related gene both was negatively glucose Biobank. In this sample, between significantly stronger than women. analysis suggested potential causal relationships fasting glucose, hr an oral tolerance test, HbA1c. Additionally, Cd300lg responded mouse model, signs impaired male, not female, knockout mice. Our study identified several novel whose change response prolonged composition, homeostasis. increased is link improved levels. may be promising biomarker therapeutic target diabetes. South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes' legat til forskning og bekjempelse av sukkersyke. Biobank resource reference 53641. Australian National Medical Research Council Investigator Grant (APP2017942). Discovery Early Career Award (DE220101226). (Project grant: 325640 Mobility 287198). Student Program at University Oslo. Novo Nordisk Fonden Excellence Emerging Endocrinology Metabolism 2023 (NNF23OC0082123). clinicaltrials.gov: NCT01803568.

Language: Английский

---