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PURPOSE: Gum chewing stimulates the sympathetic nervous system and increases energy consumption. However, the effect of mastication on physical activity remains unclear. This study aimed to investigate the effect of gum masticatory movement on physiological markers related to walking and muscle activation during cycling in different patient groups.METHODS: Using a randomized crossover design, 25 participants participated in walking trials with a 1-week washout; the trials included chewing gum (GUM), taking a candy with the same ingredients as the gum (CAN), and no ingestion (CON). Energy expenditure (EE), metabolic equivalent (MET), oxygen consumption (VO2), and heart rate were measured using a portable metabolic device. The walking distance was also calculated. In the cycling experiment, the other 19 participants randomly completed 7 minutes of the three trials (GUM, CAN, CON) with a 15-minute break. The mean cycling period (MCP), cycle number (CN), coefficient of variation of the cycling period (CV), and integrated electromyography (iEMG) results were measured using the Delsys Trigno™ Wireless EMG System.RESULTS: The walking distance was significantly higher in the GUM group than in the CAN and CON groups by an average of 78 m (7.4%, p2 demonstrated a partially significant increase after 15 minutes. In the cycling experiment, there were no significant differences in the effects of the trials on cycling performance (MCP, CN, CV). However, significant differences were observed in the GUM group for the iEMG results.CONCLUSIONS: Our study results suggest that gum chewing improves physical performance, such as walking distance, and improves energy metabolism, such as EE and METs. Additionally, it can influence the improvement in the lower limb muscle activity during cycling.

AMP-activated protein kinase (AMPK), a highly conserved, heterotrimeric serine/threonine kinase with critical sensory and regulatory functions, is proposed to induce antiaging actions of caloric restriction (CR). Although earlier studies assessed CR’s effects on AMPK in rodent skeletal muscle, the scope of these studies was narrow with a limited focus on older animals. This study’s purpose was to fill important knowledge gaps related to CR’s influence on AMPK in skeletal muscle of older animals. Therefore, using epitrochlearis muscles from 24-month-old ad-libitum fed (AL) and CR (consuming 65% of AL intake for 8 weeks), male Fischer-344 × Brown Norway F1 rats, we determined: (a) AMPK Thr172 phosphorylation (a key regulatory site) by immunoblot; (b) AMPKα1 and AMPKα2 activity (representing the 2 catalytic α-subunits of AMPK), and AMPKγ3 activity (representing AMPK complexes that include the skeletal muscle-selective regulatory γ3 subunit) using enzymatic assays; (c) phosphorylation of multiple protein substrates that are linked to CR-related effects (acetyl-CoA carboxylase [ACC], that regulates lipid oxidation; Beclin-1 and ULK1 that are autophagy regulatory proteins; Raptor, mTORC1 complex protein that regulates autophagy; TBC1D1 and TBC1D4 that regulate glucose uptake) by immunoblot; and (d) ATP and AMP concentrations (key AMPK regulators) by mass spectrometry. The results revealed significant CR-associated increases in the phosphorylation of AMPKThr172 and 4 AMPK substrates (ACC, Beclin-1, TBC1D1, and TBC1D4), without significant diet-related differences in ATP or AMP concentration or AMPKα1-, AMPKα2-, or AMPKγ3-associated activity. The enhanced phosphorylation of multiple AMPK substrates provides novel mechanistic insights linking AMPK to functionally important consequences of CR.

Background : Exercise and high fat, high sucrose restriction diets are well known treatments for obesity. The aim of this study was to measure the effects of those lifestyle interventions on molecular transducers of exercise, such as Nr4a3, mitochondria-associated proteins, and muscle function. Methods : We conducted 8 weeks of treadmill exercise and sucrose or fat restriction diets in obese mice. The mice were divided into eight groups: the normal diet (CON) group, normal diet with exercise (CONEX) group, high fat, high sucrose diet (HFHS) group, HFHS with exercise (HFHSEX) group, sucrose restriction (SR) group, SR with exercise (SREX) group, high fat, high sucrose restriction (ND) group, and ND with exercise (NDEX) group. Results : The 8 weeks of exercise reduced body weight, improved lipid profiles (total cholesterol, triglycerides), and increased hanging time. The combination of exercise and a fat and sucrose restriction diet improved glucose tolerance and increased grip strength. The 8 weeks of intervention did not significantly affect the Nr4a3 protein level. The sucrose and fat restriction diet increased the phosphorylated protein kinase B (pAkt)/Akt ratio, and its level was lower in the HFHS group. Exercise increased the protein expression level of PGC-1α in obese conditions. Moreover, SR led reduced the phosphorylated AMP-activated protein kinase (pAMPK)/AMPK ratio and PGC-1α to the control level. Conclusion : The 8 weeks of exercise or a sucrose and fat restriction diet improved metabolic indicators and muscle function. SR reduced pAMPK/AMPK and PGC-1α to the control level. Nr4a3 protein expression was not significantly changed by either exercise or a fat and sucrose restriction diet.

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.

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. 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. 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. 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.

One exercise session can elevate insulin-stimulated glucose uptake (ISGU) in skeletal muscle, but the mechanisms remain elusive. Circumstantial evidence suggests a role for Akt substrate of 160 kDa (AS160 or TBC1D4). We used genetic approaches to rigorously test this idea. The initial experiment evaluated AS160’s role for the postexercise increase in ISGU using muscles from male wildtype (WT) and AS160-knockout (AS160-KO) rats. The next experiment used AS160-KO rats with an adeno-associated virus (AAV) approach to determine if rescuing muscle AS160 deficiency could restore exercise’s ability to improve ISGU. The third experiment tested if eliminating the muscle GLUT4 deficit in AS160-KO rats via AAV-delivered GLUT4 would enable postexercise enhancement of ISGU. The final experiment employed AS160-KO rats and AAV-delivery of AS160 mutated to prevent phosphorylation of Ser588, Thr642, and Ser704 to evaluate their role in postexercise ISGU. We discovered: 1) AS160 expression was essential for postexercise increase in ISGU; 2) rescuing muscle AS160 expression of AS160-KO rats restored postexercise enhancement of ISGU; 3) restoring GLUT4 expression in AS160-KO muscle did not rescue the postexercise increase in ISGU; and 4) although AS160 phosphorylation on 3 key sites was not required for postexercise elevation in ISGU, it was essential for the full-exercise effect.

One exercise session can elevate insulin-stimulated glucose uptake (ISGU) in skeletal muscle, but the mechanisms remain elusive. Circumstantial evidence suggests a role for Akt substrate of 160 kDa (AS160 or TBC1D4). We used genetic approaches to rigorously test this idea. The initial experiment evaluated the role of AS160 in postexercise increase in ISGU using muscles from male wild-type (WT) and AS160-knockout (KO) rats. The next experiment used AS160-KO rats with an adeno-associated virus (AAV) approach to determine if rescuing muscle AS160 deficiency could restore the ability of exercise to improve ISGU. The third experiment tested if eliminating the muscle GLUT4 deficit in AS160-KO rats via AAV-delivered GLUT4 would enable postexercise enhancement of ISGU. The final experiment used AS160-KO rats and AAV delivery of AS160 mutated to prevent phosphorylation of Ser588, Thr642, and Ser704 to evaluate their role in postexercise ISGU. We discovered the following: 1) AS160 expression was essential for postexercise increase in ISGU; 2) rescuing muscle AS160 expression of AS160-KO rats restored postexercise enhancement of ISGU; 3) restoring GLUT4 expression in AS160-KO muscle did not rescue the postexercise increase in ISGU; and 4) although AS160 phosphorylation on three key sites was not required for postexercise elevation in ISGU, it was essential for the full exercise effect.

[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.

PURPOSE The purpose of this study was to examine the infancy changes of metabolic gene expression level in mouse gastrocnemius muscle after after 1 hour acute treadmill exercise. METHODS C57BL/6 mouse were randomly divided into control (n=5) and 1 hour acute treadmill exercise intervention group (n=5). After the intervention, we extracted total mRNA from the mouse gastrocnemius following the whole set of genes were analyzed by microarray using Affymetrix GeneChip Clariom_S_Mouse Array. The significantly meaningful differentially expressed genes (DEGs) were extracted and compared with the bioinformatic tools. Further analysis of DEGs were conducted using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology database. Significant cut-off by Fold change and LPE test were used as statistical test. RESULTS Fifty six upregulated and 65 downregulated DEGs were identified after the 1 hour of treadmill exercise. Nr4a3, Nr4a2, Btg2, Otud1, Sik1, Thbs1, Irs2 were included in the top 10 upregulated genes and Ube2l6, Scd3 were one of the most downregulated genes in the DEGs. In gene ontology analysis, metabolic process (>70 counts), organic substance metabolic process (>70) and cellular metabolic process (>60) were in the top 10 terms in the category of biological process. In the molecular function category, binding and protein binding term had more than 80s and 60s count genes each and they were statistically significant (p≤.001) with located on first and second place. In KEGG pathway enrichment analysis, many DEGs were related to MAPK signaling pathway, AMPK signaling pathway, Metabolic pathway, Protein processing in endoplasmic reticulum and Glycolysis/gluconeogenesis pathway. Also, several DEGs (HK1, HK2, Adh1 etc.) related to metabolism were statistically significant. CONCLUSIONS One hour acute treadmill exercise could sufficiently change some energy metabolism and adaptation related genes in mouse gastrocnemius muscle. In this microarray analysis, Nr4a3, Nr4a2, Btg2, Otud1, Sik1, Thbs1, Irs2, Ube2l6, and Scd3 were newly categorized as DEGs in respect of energy metabolism.

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., Exercise upregulated DBHB level in skeletal muscle in mice and skeletal muscle cell. Also, DBHB effected to cognitive function as well.

Although several evidence has suggested the impact of exercise on the prevention of aging phenotypes, few studies have been conducted on the mechanism by which exercise alters the immune-cell profile, thereby improving metabolism in senile obesity. In this study, we confirmed that 4-week treadmill exercise sufficiently improved metabolic function, including increased lean mass and decreased fat mass, in 88-week-old mice. The expression level of the senescence marker p16 in the white adipose tissue (WAT) was decreased after 4-weeks of exercise. Exercise induced changes in the profiles of immune-cell subsets, including natural killer (NK) cells, central memory CD8+ T cells, eosinophils, and neutrophils, in the stromal vascular fraction of WAT. In addition, it has been shown through transcriptome analysis of WAT that exercise can activate pathways involved in the interaction between WAT and immune cells, in particular NK cells, in aged mice. These results suggest that exercise has a profound effect on changes in immune-cell distribution and senescent-cell scavenging in WAT of aged mice, eventually affecting overall energy metabolism toward a more youthful state.

[Purpose] Although it is known that exercise induces angiogenesis, a clear mechanism has remained elusive due to various experimental limitations. This review presents the current status of angiogenesis-related experiments and future directions of experimentation in relation to exercise, aging, and cancer. [Methods] We conducted a PubMed search of the available literature to identify reported exercise related changes of angiogenic factors obtained in vitro using C2C12 cells and endothelial cells, and in vivo using animal experiments and in clinical studies. [Results] Exercise induced angiogenesis under normal conditions. Aging decreased angiogenic factors and increased during exercise. On the other hand, in cancer, the results indicate that angiogenic factors tend to increase in general, and that the effects of exercise need to be studied more. The exact mechanism remains unclear. [Conclusion] The effect of exercise on angiogenesis appears positive. Both resistance and aerobic exercise have positive effects, but many evidences suggest that the effects are more pronounced with aerobic exercise. Further research on the precise mechanism(s) is necessary. It is expected that these studies will include models of aging and cancer.

Background : Autophagy maintains metabolic homeostasis of muscles, and its impairment may cause muscle dysfunction. Exercise can improve muscle dysfunction induced by long-term high-fat diet. This study aimed to explore the association of autophagy with impaired muscle dysfunction in obese conditions and investigate its relationship with exercise-induced muscle function improvement. Methods : Male C57BL/6 mice (n=24) were randomly assigned to four groups: low-fat diet+plain water feeding sedentary (CON) group, low-fat diet+plain water feeding exercise (CON+EX) group, high-fat high-sucrose (HFHS) diet-fed sedentary group, and HFHS diet-fed exercise (HFHS+EX) group, and subjected to a single bout of exhaustive exercise. Results : HFHS diet resulted in shorter hanging time, reduced grip force, and lower exhaustion time and distance, and decreased lean mass per body weight. Moreover, in the soleus, which is chosen as a representative red (oxidative) muscle, LC3II/LC3I ratio, P62, and Bnip3 levels were altered following the HFHS diet, and were negatively correlated with muscle performance parameters; exercise significantly decreased the LC3II/LC3 ratio while P62 increased with HFHS diet. Autophagy-related protein changes were not found in the white (glycolytic) gastrocnemius. Conclusion : The study revealed that 20-week HFHS diet causes a significant increase in body weight and fat mass, along with a decrease in muscle function. Autophagy-related LC3 and P62 protein expression was negatively correlated with muscle function, and they were reduced when a single bout of exercise stimulated the soleus of obese mice. However, no change of autophagy-related proteins was seen in the gastrocnemius.

Tight junction protein is representative regulator of gut permeability. Also, it has been noted for controlling inflammatory responses through tight junction. Therefore, in this study, we examined that whether tight junction protein is changed in aged mice, and to further, confirmed the effect of treadmill exercise on the tight junction protein. In in vitro study, doxorubicin that induces cell senescence was treated to Caco2 cells (colon cell) to mimic aging effect. After that, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), exercise mimic chemical that stimulates AMPK level, was also administered to Caco2 cells. In animal study, 2 months and 21 months C57BL/6 J mouse were treated with treadmill exercise for 4 weeks (YE = 5, OE = 5). Then, the tight junction protein expression level was examined by western blot. Also, serum lipopolysaccharide (LPS) and zonulin level were analyzed to identify gut permeability. In vitro studies showed that doxorubicin downregulates tight junction protein expression levels in Caco2 cell, and also AICAR treatment upregulates tight junction protein expression levels. In animal study, 4 weeks treadmill exercise upregulated claudin-1 (p 0.05) and occludin (p 0.01) protein expression level in 21 months old mice. Also, zonula occluden-1 (ZO-1) protein expression level was not significant difference among all mice group. In addition, old mice group had higher level of serum LPS compared to young mice group, but the level was downregulated in both 2 months and 21 months mice group after four weeks of treadmill exercise. Zonulin, which is known as degrading tight junction protein, is not significantly changed by both age and exercise. This study compared that tight junction protein expression level in old mice compared to its level in young mice, and also clarified that the effect of treadmill exercise on tight junction protein in both young and old mice.