Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation.

Fibroblast growth factor 21, a metabolic regulator, plays roles in lipolysis and glucose uptake in adipose tissues and skeletal muscles. Its expression in skeletal muscle is upregulated upon activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, which is induced by exercise and muscle contraction. We examined the increase of fibroblast growth factor 21 after acute exercise in metabolic organs, especially skeletal muscles and circulation. Participants exercised on bicycle ergometers for 60 min at 75% of their V˙O2max. Venous blood samples were taken before exercise and immediately after exercise. In an animal study, male ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed treadmill exercises at 30 m min(-1) for 60 min. Shortly thereafter, blood, liver, and skeletal muscle samples were taken from mice. Acute exercise induced the increase of serum fibroblast growth factor 21 in both humans and mice, and increased fibroblast growth factor 21 expression in the skeletal muscles and the liver of mice. Acute exercise activated Akt in mice skeletal muscle. Acute exercise increases fibroblast growth factor 21 concentrations in both serum and metabolic organs. Moreover, results show that acute exercise increased the expression of fibroblast growth factor 21 in skeletal muscle, accompanied by the phosphorylation of Akt in mice.

Effect of low glycemic index food and postprandial exercise on blood glucose level, oxidative stress and antioxidant capacity.

Low glycemic index (GI) food and postprandial exercise are non-drug therapies for improving postprandial hyperglycemia. The present randomized, crossover study investigated the effect of low GI food combined with postprandial exercise on postprandial blood glucose level, oxidative stress and antioxidant capacity. A total of 13 healthy subjects were each used in four experiments: i) rice only (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and iv) salad prior to rice and exercise following rice (MIX). The blood glucose level, oxidative stress and antioxidant capacity were then measured. At 60 min after the meal, the blood glucose level was observed to be increased in the MIX group compared with that in the LGI group. Furthermore, at 180 min, the antioxidant capacity was found to be reduced in the MIX group compared with those of the LGI and EX groups. These findings suggest that low GI food combined with postprandial exercise does not improve postprandial hyperglycemia. It may be necessary to establish optimal timing and intensity when combining low GI food with postprandial exercise to improve postprandial hyperglycemia.

A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise.

OBJECTIVE: Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis. METHODS: To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments. RESULTS: A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells. CONCLUSIONS: These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.

Dietary whey hydrolysate with exercise alters the plasma protein profile: a comprehensive protein analysis.

OBJECTIVE: It has been shown that dietary whey protein accelerates glucose uptake by altering glycoregulatory enzyme activity in skeletal muscle. In the present study, we investigated the effect of dietary whey protein on endurance and glycogen resynthesis and attempted to identify plasma proteins that reflected the physical condition by a comprehensive proteomics approach. METHODS: Male c57BL/6 mice were divided into four groups: sedentary, sedentary with whey protein hydrolysate, exercise, and exercise with whey protein hydrolysate. The mice in the exercise groups performed treadmill running exercise five times per week for 4 wk. Protein profiling of plasma sample obtained from individuals was performed, as were measurements of endurance performance and the glycogen content of gastrocnemius muscle. RESULTS: After the training period, the endurance of mice fed the whey diet was improved compared with that of mice fed the control diet. Muscle glycogen content was significantly increased after 4 wk of exercise, and intake of whey protein led to a further increase in glycogen. Apolipoproteins A-II and C-I and ß(2)-glycoprotein-1 were found to be altered by training combined with the intake of whey protein, without significant changes induced by exercise or whey protein alone. CONCLUSION: Results of the present study suggest that these three proteins may be potential biomarkers of improved endurance and glycogen resynthesis and part of the mechanism that mediates the benefits of whey protein.

Regular exercise reduces colon tumorigenesis associated with suppression of iNOS.

Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the mechanism involved is unclear. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) is often elevated in an initial step of tumorigenesis and promotes colorectal cancer. We investigated the effect of exercise on colon tumorigenesis associated with iNOS and COX-2 in azoxymethan (AOM)-injected mice. Balb/c mice (8 weeks old) were divided into three groups of 20 animals each, consisting of a sedentary control group, an AOM group, and an exercise plus AOM group. Mice in the groups receiving AOM were injected intraperitoneally with AOM weekly for 2 weeks. Six weeks of regular exercise suppressed the generation of aberrant crypt foci (ACF) in the colon by AOM. Expression of iNOS was decreased by exercise compared with that in sedentary mice along with lower nitrotyrosine level while COX-2 was not changed by either AOM or exercise. Additionally, tumor necrosis factor alpha (TNFalpha) was decreased by exercise in the colon and plasma. There was no effect of exercise on the expression of antioxidant enzymes and chaperon protein in the colon. Our results suggest that regular exercise prevents colon tumorigenesis, at least partly via the suppression of iNOS expression associated with anti-inflammation.

The microRNA miR-696 regulates PGC-1{alpha} in mouse skeletal muscle in response to physical activity.

MicroRNAs (miRNAs) are small noncoding RNAs involved in posttranscriptional gene regulation that have been shown to be involved in growth, development, function, and stress responses of various organs. The purpose of this study was to identify the miRNA response to physical activity, which was related to functions such as nutrient metabolism, although the miRNAs involved are currently unknown. C57BL/6 mice were divided into exercise and control groups. The exercise group performed running exercise, with a gradual increase of the load over 4 wk. On the other hand, to examine the effect of muscle inactivity, the unilateral hindlimbs of other mice were fixed in a cast for 5 days. Microarray analysis for miRNA in gastrocnemius revealed that miR-696 was markedly affected by both exercise and immobilization, showing opposite responses to these two interventions. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), which was increased by exercise and decreased by immobilization in the protein level, was predicted as a target regulated by miR-696. In cultured myocytes, intracellular miR-696 variation led to negative regulation of PGC-1alpha protein along with the expression of mRNAs for downstream genes. In addition, we found decreases in the biogenesis of mitochondria and fatty acid oxidation in miR-696-overexpressing myocytes compared with normal control myocytes. These observations demonstrate that miR-696 is a physical activity-dependent miRNA involved in the translational regulation of PGC-1alpha and skeletal muscle metabolism in mice.

Relaxant effect of microtitan via regulation of autonomic nerve activity in mice.

AIMS: It has been shown that microtitan may possibly affect the nervous system. In the present study, we examined the effect of microtitan on spontaneous activity during the sleeping period and on autonomic nervous activity in mice. MAIN METHODS: Institute of Cancer Research (ICR) mice were divided into placebo and microtitan groups that were housed in chambers with rubber sheets impregnated with microtitan or placebo sheets. In both groups, spontaneous active movement, metabolic parameters, and heart rate variability (HRV) were measured. KEY FINDINGS: Spontaneous activity during the light period was decreased for mice housed with microtitan sheets compared with placebo sheets. The urinary noradrenalin level was also reduced by microtitan. Heart rate variability was assessed by using a telemetry system and autonomic nervous activity was estimated. Power spectral analysis of R-R interval data revealed that the high frequency band, which shows parasympathetic activity, was significantly increased by microtitan, while the low frequency to high frequency power spectral ratio was decreased in the mice housed with microtitan sheets compared to the mice housed with placebo sheets. SIGNIFICANCE: Microtitan promoted rest during the sleeping period by regulating autonomic nervous activity, which indicates that microtitan has a relaxant effect.

Azuki bean juice lowers serum triglyceride concentrations in healthy young women.

Effects of azuki bean juice supplementation, prescribed according to a Kanpo medicine regimen, on serum lipid concentrations were studied. Healthy young Japanese women were recruited and were randomly assigned to one of the three groups using a parallel-group design. Control (n = 10), azuki (n = 11) and Concentrated azuki (CA) (n = 12) juice groups consumed 150 g daily of the isocaloric assigned juice for one menstrual cycle with their usual diet. Triglyceride concentrations were decreased in the azuki juice group (p<0.05) and tended to be decreased in the CA juice group (p = 0.055). Triglyceride concentrations in the azuki and CA juice groups decreased by 0.170 mmol/liter (15.4%) and 0.159 mmol/liter (17.9%), respectively (p<0.05). The azuki and CA juice used in this study inhibited pancreatic lipase activity 29.2% and 56.9%, respectively, in vitro. Lipid peroxide changes, based on ANCOVA with the initial level and alpha-tocopherol changes as covariates, did not differ among the three groups. Serum low density lipoprotein-cholesterol and high density lipoprotein-cholesterol (HDL) cholesterol concentrations did not change. Thus, azuki bean juice intake, as a traditional Kampo prescription, might be beneficial for preventing hypertriglyceridemia.

Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification.

Intracellular redox balance may affect nutrient metabolism in skeletal muscle. Astaxanthin, a carotenoid contained in various natural foods, exerts high antioxidative capacity in the skeletal muscles. The present study investigated the effect of astaxanthin on muscle lipid metabolism in exercise. ICR mice (8 weeks old) were divided into four different groups: sedentary, sedentary treated with astaxanthin, running exercise, and exercise treated with astaxanthin. After 4 weeks of treatment, exercise groups performed treadmill running. Astaxanthin increased fat utilization during exercise compared with mice on a normal diet with prolongation of the running time to exhaustion. Colocalization of fatty acid translocase with carnitine palmitoyltransferase I (CPT I) in skeletal muscle was increased by astaxanthin. We also found that hexanoyl-lysine modification of CPT I was increased by exercise, while astaxanthin prevented this increase. In additional experiment, we found that astaxanthin treatment accelerated the decrease of body fat accumulation with exercise training. Our results suggested that astaxanthin promoted lipid metabolism rather than glucose utilization during exercise via CPT I activation, which led to improvement of endurance and efficient reduction of adipose tissue with training.

Oxidative stress and delayed-onset muscle damage after exercise.

Reactive oxygen species (ROS) produced during exercise may be involved in delayed-onset muscle damage related to inflammation. To investigate this hypothesis, we studied whether oxidative stress increases nuclear translocation of nuclear factor-kappaB and chemokine expression in skeletal muscle using myotube L6 cells. We also assessed whether prolonged acute exercise could increase these parameters in rats. In L6 cells, H(2)O(2) induced nuclear translocation of p65 and increased the expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and monocyte chemoattractant protein-1 (MCP-1), whereas preincubation with alpha-tocopherol limited the increase in these proteins. Sprague Dawley rats were divided into the following groups: rested control, exercised, rested with a high alpha-tocopherol diet, and exercised with a high alpha-tocopherol diet. After 3 weeks of acclimation, both exercise groups ran on a treadmill at 25 m/min for 60 min. Exercise increased nuclear p65, CINC-1, and MCP-1 in gastrocnemius muscle cells, but these changes were ameliorated by the high alpha-tocopherol diet. Increases in myeloperoxidase and thiobarbituric acid-reactive substrates were ameliorated by a high alpha-tocopherol diet, as were the histological changes. Neutrophil activity was not altered by either exercise or a high alpha-tocopherol diet. These results indicate that delayed-onset muscle damage induced by prolonged exercise is partly related to inflammation via phagocyte infiltration caused by ROS and that alpha-tocopherol (an antioxidant) can attenuate such inflammatory changes.