Deep-learning model for predicting physical fitness in possible sarcopenia: analysis of the Korean physical fitness award from 2010 to 2023.

Introduction: Physical fitness is regarded as a significant indicator of sarcopenia. This study aimed to develop and evaluate a deep-learning model for predicting the decline in physical fitness due to sarcopenia in individuals with potential sarcopenia. Methods: This study used the 2010-2023 Korean National Physical Fitness Award data. The data comprised exercise- and health-related measurements in Koreans aged >65 years and included body composition and physical fitness variables. Appendicular muscle mass (ASM) was calculated as ASM/height2 to define normal and possible sarcopenia. The deep-learning model was created with EarlyStopping and ModelCheckpoint to prevent overfitting and was evaluated using stratified k-fold cross-validation (k = 5). The model was trained and tested using training data and validation data from each fold. The model's performance was assessed using a confusion matrix, receiver operating characteristic curve, and area under the curve. The average performance metrics obtained from each cross-validation were determined. For the analysis of feature importance, SHAP, permutation feature importance, and LIME were employed as model-agnostic explanation methods. Results: The deep-learning model proved effective in distinguishing from sarcopenia, with an accuracy of 87.55%, precision of 85.57%, recall of 90.34%, and F1 score of 87.89%. Waist circumference (WC, cm), absolute grip strength (kg), and body fat (BF, %) had an influence on the model output. SHAP, LIME, and permutation feature importance analyses revealed that WC and absolute grip strength were the most important variables. WC, figure-of-8 walk, BF, timed up-and-go, and sit-and-reach emerged as key factors for predicting possible sarcopenia. Conclusion: The deep-learning model showed high accuracy and recall with respect to possible sarcopenia prediction. Considering the need for the development of a more detailed and accurate sarcopenia prediction model, the study findings hold promise for enhancing sarcopenia prediction using deep learning.

Prediction models of grip strength in adults above 65 years using Korean National Physical Fitness Award Data from 2009 to 2019.

PURPOSE: We aimed to determine the best machine learning (ML) regression model for predicting grip strength in adults above 65 years using various independent variables, such as body composition, blood pressure, and physical performance. METHODS: The data comprised 107,290 participants, of whom 33.3% were male and 66.7% were female in Korean National Fitness Award Data from 2009 to 2019. The dependent variable was grip strength, which was calculated as the mean of right and left grip strength values. RESULTS: The results showed that the CatBoost Regressor had the lowest mean squared error (M [Formula: see text] SE:16.659 ± 0.549) and highest R2 value (M [Formula: see text] SE:0.719 ± 0.009) among the seven prediction models tested. The importance of independent variables in facilitating model learning was also determined, with the Figure-of-8 walk test being the most significant. These findings suggest that walking ability and grip strength are closely related, and the Figure-of- 8 walk test is a reasonable indicator of grip strength in older adults. CONCLUSION: The findings of this study can be used to develop more accurate predictive models of grip strength in older adults.

The Potential Roles of Myokines in Adipose Tissue Metabolism with Exercise and Cold Exposure.

Exercise and cold exposure are two stimuli that have been suggested as solely effective to modulate adipose tissue metabolism and improve metabolic health in obese populations. The two primary organs involved in energy metabolism during exercise and/or cold exposure are skeletal muscle and adipose tissue. Adipose tissue can be divided mainly into two types: white adipose tissue (WAT), which primarily stores energy, and brown adipose tissue (BAT), known as the primary source of thermogenesis. The exercise-stimulated release of myokines allows for crosstalk between skeletal muscle and adipose tissue, partially mediating the beneficial effects of exercise. Cold exposure is another trigger for the regulation of myokine secretions, thus increasing adipose tissue metabolism, especially via activation of BAT. Therefore, this has generated the hypothesis that exercise in conjunction with cold exposure might be the optimal regimen to regulate myokine profiles and gain more beneficial health effects. However, to date, human experimental data regarding different exercise (frequency, type, time and intensity) and cold exposure (temperature, time and frequency) patterns are scarce. In this review, we will summarize the current human clinical trials investigating the regulation of myokines induced by exercise combined with cold exposure, to elaborate on the roles of myokines in mediating adipose tissue metabolism.

Dynapenic-abdominal obesity as an independent risk factor for chronic kidney disease in postmenopausal women: a population-based cohort study.

OBJECTIVE: Low muscle strength and obesity lead to a higher risk of chronic kidney disease (CKD). Perimenopause is associated with a natural decline in muscle strength and an increase in visceral adiposity. Dynapenic obesity, which is the coexistence of low muscle strength and obesity, is expected to synergistically increase the prevalence of CKD in postmenopausal women. The aim of this study was to determine combined associations of dynapenia and obesity with CKD in postmenopausal women. METHODS: This study used data from the Korean National Health and Nutrition Examination Survey, 2016 to 2019. The study included 4,525 postmenopausal women aged 42 to 80 years that were classified into four groups based on waist circumference (≥85 cm) and hand grip strength (<18 kg): normal, dynapenic, obese, or dynapenic-obese. According to the Kidney Disease: Improving Global Outcomes, we defined CKD as an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Complex sample logistic regression models were conducted to determine the relationships among coexistence of dynapenia, abdominal obesity, and the risk of CKD. RESULTS: Dynapenic-abdominal obese group displayed lower estimated glomerular filtration rate levels than other groups (P < 0.05 for all data). The prevalence rates of CKD were 15.5%, 7.8%, 6.2%, and 2.4% in the dynapenic-abdominal obese, dynapenic, abdominal obese, and normal groups, respectively (P < 0.001). Complex sample logistic regression analyses, after adjusting for age, height, health behaviors, and comorbidities, showed that the odds ratio for CKD with respect to dynapenic-abdominal obesity was 1.82 (95% confidence interval, 1.19-2.79) and to abdominal obesity was 1.54 (95% confidence interval, 1.07-2.22) than in the normal group. CONCLUSIONS: This study demonstrated that dynapenic-abdominal obesity, as determined by low handgrip strength and high waist circumference values, was associated with increased risk of CKD in postmenopausal women.

Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle.

PURPOSE: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated. METHODS: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis. RESULTS: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group. CONCLUSION: Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle.

Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats.

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagyrelated proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-weekold male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580].

Effects of exercise on AKT/PGC1-α/FOXO3a pathway and muscle atrophy in cisplatin-administered rat skeletal muscle.

Cisplatin has been reported to cause side effects such as muscle wasting in humans and rodents. The physiological mechanisms involved in preventing muscle wasting, such as the regulation of AKT, PGC1-α, and autophagy-related factor FOXO3a by MuRF 1 and Atrogin-1, remain unclear following different types of exercise and in various skeletal muscle types. Eight-week-old male Wistar rats (n = 34) were assigned to one of four groups: control (CON, n = 6), cisplatin injection (1 mg/kg) without exercise (CC, n = 8), cisplatin (1 mg/kg) + resistance exercise (CRE, n = 9) group, and cisplatin (1 mg/kg) + aerobic exercise (CAE, n = 11). The CRE group performed progressive ladder exercise (starting with 10% of body weight on a 1-m ladder with 2-cm-interval grids, at 85°) for 8 weeks. The CAE group exercised by treadmill running (20 m/min for 60 min daily, 4 times/week) for 8 weeks. Compared with the CC group, the levels of the autophagy-related factors BNIP3, Beclin 1, LC3-II/I ratio, p62, and FOXO3a in the gastrocnemius and soleus muscles were significantly decreased in the CRE and CAE groups. The CRE and CAE groups further showed significantly decreased MuRF 1 and Atrogin-1 levels and increased phosphorylation of AKT, FOXO3a, and PGC1-α. These results suggest that both ladder and aerobic exercise directly affected muscle wasting by modulating the AKT/PGC1-α/FOXO3a signaling pathways regardless of the skeletal muscle type.

Investigation of the effect of Staufen1 overexpression on the HIV-1 virus production.

In this study, we investigated how Staufen1 influences the HIV-1 production. The overexpression of Staufen1 increased virus production without any negative affect on the viral infectivity. This increase was not caused by transcriptional activation; but by influencing post-transcriptional steps. Using multiple Gag protein derivatives, we confirmed that the zinc-finger domains of the HIV-1 nucleocapsid (NC) are important for its interaction with Staufen1. We also found that Staufen1 colocalized in stress granules with the mature form of the HIV-1 NC protein. [BMB Reports 2021; 54(11): 551-556].

Effects and Moderators of Exercise on Sarcopenic Components in Sarcopenic Elderly: A Systematic Review and Meta-Analysis.

Background: Sarcopenia is a muscle disease in loss of muscle strength, mass, and function associated with aging. Although protective effects of exercise on muscle mass and function are generally recognized, research findings in sarcopenic adults are inconsistent. It is necessary to conduct a systematic review to determine the effects of exercise on muscle strength, body composition, and physical performance in older adults with sarcopenia, and to examine the potential moderators including sociodemographic characteristics and exercise-related factors. Methods: Six electronical academic databases (Medline, Embase, CINAHL, Scopus, Cochrane Library, and SPORTDiscus) were used to retrieve the eligible studies from inception to May 2020. Two reviewers independently selected and extracted the data from each included study, and effect sizes were calculated by employing random-effect models with 95% confidential interval (CI). The Physiotherapy Evidence Database (PEDro) scale was used to assess study quality. Results: Seventeen studies (985 participants with sarcopenia, aged 67.6-86 years) were included in this review study. The meta-analytic results showed significant improvements in muscle strength [grip strength, SMD = 0.30, 95% CI (0.15, 0.45), I 2 = 6%, p < 0.01; knee extension, SMD = 0.32, 95% CI (0.15, 0.50), I 2 = 0%, p < 0.01; and chair and stand, SMD = 0.56, 95% CI (0.30, 0.81), I 2 = 36%, p < 0.01], in physical performance [timed up and go, SMD = 0.74, 95% CI (0.48, 1.00), I 2 = 0%, p < 0.01; and gait speed, SMD = 0.59, 95% CI (0.35, 0.82), I 2 = 62%, p < 0.01], and in body composition [skeletal muscle mass index, SMD = 0.37, 95% CI (0.15, 0.58), I 2 = 16%, p < 0.01; and appendicular skeletal muscle, SMD = 0.31, 95% CI (0.13, 0.49), I 2 = 20%, p < 0.01]. However, there were no significant differences in other body composition (SMD = 0.20-0.36). Additionally, meta-regression revealed that the higher percent of female participants was significantly associated with improved gait speed (ß = 0.0096, p = 0.03) and decreased skeletal muscle mass index (ß = -0.0092, p = 0.01). Conclusions: The current meta-analysis suggests that exercise is a beneficial therapy, which has protective effects for older adults with sarcopenia. Some beneficial effects may be moderated by gender and exercise intensity.

The Effects of Exercise and Restriction of Sugar-Sweetened Beverages on Muscle Function and Autophagy Regulation in High-Fat High-Sucrose-Fed Obesity Mice.

BACKGROUND: Autophagy maintains muscle mass and healthy skeletal muscles. Several recent studies have associated sugar-sweetened beverage (SSB) consumption with diseases. We investigated whether muscle dysfunction due to obesity could be restored by SSB restriction (SR) alone or in combination with exercise (EX) training. METHODS: Obese mice were subjected to SR combined with treadmill EX. Intraperitoneal glucose tolerance test, grip strength test, hanging time test, and body composition analysis were performed. Triglyceride (TG) and total cholesterol (TC) serum concentrations and TG concentrations in quadriceps muscles were analyzed. Western blot and reverse transcription-quantitative polymerase chain reaction helped analyze autophagy-related protein and mRNA expression, respectively. RESULTS: SR alone had no significant effect on fasting blood glucose levels, glucose tolerance, and muscle function. However, it had effect on serum TC, serum TG, and BCL2 interacting protein 3 expression. SR+EX improved glucose tolerance and muscle function and increased serum TC utilization than SR alone. SR+EX reduced P62 levels, increased glucose transporter type 4 and peroxisome proliferator-activated receptor γ coactivator-1α protein expression, and improved grip strength relative to the high-fat and high-sucrose liquid (HFHS) group, and this was not observed in the HFHS+EX group. CONCLUSION: SR induced mitophagy-related protein expression in quadriceps, without affecting muscle function. And, the combination of SR and EX activated mitophagy-related proteins and improved muscle function.

Effects of exercise-induced beta-hydroxybutyrate on muscle function and cognitive function.

Recent studies have shown that exercise improves skeletal muscle and cognitive function by stimulating the secretion of numerous molecules. In particular, previous studies have suggested that exercise-induced beta-hydroxybutyrate (BHB) release might improve skeletal muscle and cognitive function, but to date these studies have been limited to cell and animal models. Therefore, we aimed to determine how an exercise-induced increase in BHB affects skeletal muscle and cognitive function at a cellular level, in an animal model, and in humans. The effects of BHB on skeletal muscle and cognitive function were determined by treating C2C12 and C6 cell lines with BHB, and by measuring the skeletal muscle and serum BHB concentrations in aged mice after endurance or resistance exercise. In addition, serum BHB concentration was measured before and after high-speed band exercise in elderly people, and its relationships with muscle and cognitive function were analyzed. We found that BHB increased cell viability and brain-derived neurotrophic factor expression level in C6 cells, and endurance exercise, but not resistance exercise, increased the muscle BHB concentration in aged mice. Furthermore, the BHB concentration was positively related to skeletal muscle and cognitive function. Exercise did not increase the serum BHB concentration in the elderly people and BHB did not correlate with cognitive function, but after excluding the five people with the highest preexisting serum concentrations of BHB, the BHB concentrations of the remaining participants were increased by exercise, and the concentration showed a tendency toward a positive correlation with cognitive function. Thus, the BHB released by skeletal muscle following endurance exercise may improve muscle and cognitive function in animals and humans.

Hepatokines as a Molecular Transducer of Exercise.

Exercise has health benefits and prevents a range of chronic diseases caused by physiological and biological changes in the whole body. Generally, the metabolic regulation of skeletal muscle through exercise is known to have a protective effect on the pathogenesis of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cardiovascular disease (CVD). Besides this, the importance of the liver as an endocrine organ is a hot research topic. Hepatocytes also secrete many hepatokines in response to nutritional conditions and/or physical activity. In particular, certain hepatokines play a major role in the regulation of whole-body metabolic homeostasis. In this review, we summarize the recent research findings on the exercise-mediated regulation of hepatokines, including fibroblast growth factor 21, fetuin-A, angiopoietin-like protein 4, and follistatin. These hepatokines serve as molecular transducers of the metabolic benefits of physical activity in chronic metabolic diseases, including NAFLD, T2D, and CVDs, in various tissues.

Effects of rural community-based integrated exercise and health education programs on the mobility function of older adults with knee osteoarthritis.

AIM: To examine the effects of a rural community-based program integrating health education and self-directed home-based resistance training on the mobility function of older women with knee osteoarthritis (OA). METHODS: Participants were assigned to the control (CON) or intervention (INT) group. Participants completed a mobility function assessment and questionnaire evaluation. The CON group received only the health education program and the INT group also participated in resistance training for 5 months. Primary outcomes were mobility function measured using a timed chair stand (TCS), timed up & go (TUG), gait speed (GS), and knee extensor strength (KES). We evaluated body composition and questionnaire results (WOMAC score, SARC-F scale, and SOF index) as secondary outcomes. RESULTS: There were significant differences in the interactions of group-by-time effects for TCS (p < 0.001), TUG (p = 0.006), GS (p = 0.020), and knee strength (p = 0.010). In the CON group, TCS (p = 0.003) and TUG (p = 0.005) increased compared with baseline, while in the INT group, TCS decreased significantly (p < 0.001) and TUG tended to decrease after the intervention. The INT group showed improvement in GS (p < 0.001) and KES (p = 0.003) after the intervention. By contrast, the CON group showed decreasing GS (p = 0.021) and KES (p = 0.011) compared with baseline. The SARC-F scale differed significantly in the interaction of group-by-time effects (p = 0.030), while the body composition, SOF index, and WOMAC score did not differ. CONCLUSION: These results suggest that an integrated intervention program combining self-directed home-based resistance training with health education effectively improves the mobility function of older adults with knee OA dwelling in rural areas.

Exercise-Induced Circulating Irisin Level Is Correlated with Improved Cardiac Function in Rats.

Irisin, a recently identified myokine, plays an important physiological role in modulating energy homeostasis. However, the role of irisin in cardiac function during exercise has not been evaluated. In this study, we investigated the effect of exercise on irisin, pro-inflammatory cytokines, and cardiac function during 12 weeks of exercise in rats. Eight-week-old Sprague-Dawley male rats were randomly divided into two groups (n = 9 per group): sedentary control (CON) and exercise (EXE) groups. The EXE group was trained on a motorized treadmill at 20 m/min, for 60 min/day, five times/week for 12 weeks. The EXE group showed a decrease in abdominal visceral fat (p < 0.05), epididymal fat (p < 0.01), and total cholesterol (TC) (p < 0.05) and an increase in irisin levels (p < 0.01). Irisin negatively correlated with abdominal visceral (p < 0.05) and epididymal fat (p < 0.05) and positively correlated with the ejection fraction (p < 0.05), fractional shortening (p < 0.05), and cardiac output (p < 0.05). In conclusion, exercise decreases the abdominal visceral and epididymal fat and TC levels, possibly caused by elevated irisin levels, thus improving the cardiac function. This suggests that exercise-induced circulating irisin levels correlate with improved cardiac function in rats.

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising due to diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function and calcium regulation. This review summarizes the recent scientific findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

Does exercise-induced apelin affect sarcopenia? A systematic review and meta-analysis.

PURPOSE/OBJECTIVE: There have been a number of studies on the role of the novel protein apelin, identified in 1998, in improving muscular function and structure in various human organs, as well as on how it is involved in pathological processes. The aim of this systematic review and meta-analysis was to determine the effect of exercise on serum apelin levels to provide up-to-date data for the development of an exercise intervention for older adults. METHODS: We searched for articles in PubMed, Ovid MEDLINE, and EMBASE from database inception to May 31, 2019. To conduct a meta-analysis of the primary outcome (serum apelin level), we analyzed intervention effect sizes of the differences between the exercise group and control groups for the primary outcome measure at post-treatment. The outcomes were analyzed using Hedge's statistic effect size (Zr) for weight mean difference (WMD) from various statistical results, including t, F, x2, and r. A heterogeneity test was conducted using Higgin's I2 statistic and Q statistics (p > 0.10) via a forest plot. A fixed-effect model was considered if Higgin's I2 was less than 50%. If heterogeneity was high (I2 > 50%), a random-effects model with a subgroup analysis or meta-regression was used. A meta-analysis using nine studies showed that exercise could increase serum apelin levels, which was beneficial for such metabolic diseases as diabetes. RESULTS: In the subgroup analysis, the 50-60-year-old group showed significant effects of exercise. However, the BMI (normal, overweight, and obesity) categories failed to show any difference in exercise-induced effect. CONCLUSION: Further studies are needed to clarify in greater detail the effect of resistance exercise on apelin levels, including data on frequency, type, intensity, and time of aerobic exercise, to compare their effects on sarcopenia and cognitive disorders.

In Staphylococcus aureus, the Particulate State of the Cell Envelope Is Required for the Efficient Induction of Host Defense Responses.

Upon microbial infection, host immune cells recognize bacterial cell envelope components through cognate receptors. Although bacterial cell envelope components function as innate immune molecules, the role of the physical state of the bacterial cell envelope (i.e., particulate versus soluble) in host immune activation has not been clearly defined. Here, using two different forms of the staphylococcal cell envelope of Staphylococcus aureus RN4220 and USA300 LAC strains, we provide biochemical and immunological evidence that the particulate state is required for the effective activation of host innate immune responses. In a murine model of peritoneal infection, the particulate form of the staphylococcal cell envelope (PCE) induced the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and CC chemokine ligand 2 (CCL2), the chemotactic cytokines for neutrophils and monocytes, respectively, resulting in a strong influx of the phagocytes into the peritoneal cavity. In contrast, compared with PCE, the soluble form of cell envelope (SCE), which was derived from PCE by treatment with cell wall-hydrolyzing enzymes, showed minimal activity. PCE also induced the secretion of calprotectin (myeloid-related protein 8/14 [MRP8/14] complex), a phagocyte-derived antimicrobial protein, into the peritoneal cavity at a much higher level than did SCE. The injected PCE particles were phagocytosed by the infiltrated neutrophils and monocytes and then delivered to mediastinal draining lymph nodes. More importantly, intraperitoneally (i.p.) injected PCE efficiently protected mice from S. aureus infection, which was abolished by the depletion of either monocytes/macrophages or neutrophils. This study demonstrated that the physical state of bacterial cells is a critical factor for efficient host immune activation and the protection of hosts from staphylococcal infections.

Potential role of exercise-induced glucose-6-phosphate isomerase in skeletal muscle function.

PURPOSE: Recent studies have shown that glucose-6-phosphate isomerase (GPI)-which is a glycolysis interconversion enzyme-reduces oxidative stress. However, these studies are limited to tumors such as fibrosarcoma, and there are no studies that have examined the effects of exercise on GPI expression in mice skeletal muscle. Furthermore, GPI acts in an autocrine manner thorough its receptor, autocrine motility factor receptor (AMFR); therefore, we investigated expression level changes of secreted GPI from skeletal muscle in in vitro study to examine the potential role of GPI on skeletal muscle. METHODS: First, we performed an in vitro study, to identify the condition that upregulates GPI levels in skeletal muscle cells; we treated C2C12 muscle cells with an exercise-mimicking chemical, AICAR. AICAR treatment upregulated GPI expression level in C2C12 cell and its secretomes. To confirm the direct effect of GPI on skeletal muscle cells, we treated C2C12 cells with GPI recombinant protein. RESULTS: We found that GPI improved the viability of C2C12 cells. In the in vivo study, the exercise-treated mice group showed upregulated GPI expression in skeletal muscle. Based on the in vitro study results, we speculated that expression level of GPI in skeletal muscle might be associated with muscle function. We analyzed the association between GPI expression level and the grip strength of the all mice group. The mice group's grip strengths were upregulated after 2 weeks of treadmill exercise, and GPI expression level positively correlated with the grip strength. CONCLUSION: These results suggested that the exercise-induced GPI expression in skeletal muscle might have a positive effect on skeletal muscle function.