Peroxisomal proliferator-activated receptor gamma co-activator-1 alpha gene expression increases above the lactate threshold in human skeletal muscle.

AIM: Peroxisomal proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) plays a role not only as an activator of mitochondrial biogenesis, but also as a suppressor of inflammatory cytokines, which induce chronic diseases. Therefore, increasing PGC-1α expression can be one of the important factors for preventing chronic diseases. PGC-1α expression is activated by adenosine monophosphate-activated protein kinase (AMPK) and cAMP dependent kinase. The activity of these enzymes depends on the exercise intensity. Therefore, this study compared the effects of two different exercise intensities (above lactate threshold (LT) and below LT) with an equal amount of energy expenditure on PGC-1α gene expression in human skeletal muscle. METHODS: Six young men participated in this study. They performed exercise at 120% and 80% LT intensity. The duration of the 120% LT exercise was 60 minutes and the duration of the session performed at 80% LT was calculated to yield equal energy expenditure as the 120% LT intensity exercise. Skeletal muscle was obtained after 1 hour of exercise. RESULTS: The working rate, % peak VO2 and HR during exercise were significantly higher in at 120% LT than at 80% LT. PGC-1α gene expression was not significantly different between control (0.087; 0.026-0.284 (the median; inter quartile range)) and 80% LT (0.171; 0.030-0.484). However, PGC-1α gene expression after 120% LT (0.441; 0.121-4.643) was significantly higher than in the control. CONCLUSION: The findings of this study suggest that PGC-1α gene expression depends on exercise intensity.

Physical function is weakly associated with angiotensin-converting enzyme gene I/D polymorphism in elderly Japanese subjects.

BACKGROUND: The turning point in the deterioration of physical function seems to occur between the ages of 70 and 80 years. In particular, muscle strength may decline even more in subjects older than 75. A recent study found that the angiotensin-converting enzyme (ACE) genotype also affects physiological left ventricular hypertrophy. A very limited number of papers have examined genetic differences in resistance and endurance forms of a single sporting discipline. OBJECTIVE: The purpose of this study was to evaluate the relationship between ACE genotype and physical function by controlling the known confounding factors including dental status. METHODS: We selected 431 subjects who were aged 76 years and did not require special care for their daily activities. We conducted a medical examination, followed by 5 physical function tests, as follows: (1) maximum hand grip strength, (2) maximal isometric knee extensor strength, (3) maximal stepping rate for 10 s, (4) one-leg standing time with eyes open and (5) 10-meter maximum walking speed. Subjects were genotyped for the ACE intron 16 Alu insertion. In addition, serum concentrations of total cholesterol, total protein, IgA and IgG were measured at a commercial laboratory. The Eichner index was used as an indicator of occlusal condition. Multiple linear regression analysis was performed to evaluate the relationship between the ACE gene insertion/deletion (I/D) polymorphism and physical function considering confounding factors. RESULTS: The ACE gene I/D polymorphism was positively associated with hand grip strength and 10-meter maximum walking speed. Betas of hand grip strength were 0.09 for I/D (p = 0.022) and 0.12 for insertion/insertion (I/I; p = 0.004). Betas of 10-meter walking speed were -0.11 for I/D (p = 0.093) and -0.14 for I/I (p = 0.039). Dental status such as Eichner index class C was significantly associated with one-leg standing time with eyes open (beta -0.11; p = 0.028). CONCLUSION: This study suggests that there is a significant relationship between ACE genotype and physical function. In particular, subjects with the ACE deletion/deletion genotype were associated with upper extremities.

The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle.

The insertion (I) allele of the human angiotensin-converting enzyme (ACE) gene is associated with lower serum and tissue ACE activity, and with greater endurance performance and enhanced mechanical efficiency of trained muscle. We tested the hypothesis that the ACE-I allele may be associated with increased slow-twitch fiber, which is more efficient than fast-twitch fiber in low-velocity contraction, by examining the association between the ACE genotype and skeletal muscle fiber (SMF) types in 41 untrained healthy young volunteer subjects (31 males, 10 females, age 24 +/- 3 years). Skeletal muscle samples were taken from the left vastus lateralis using the needle-biopsy method. Slow-twitch type I fibers and fast-twitch type IIa and IIb fibers were classified histochemically based on staining for myosin adenosine triphosphatase (ATPase) activity at different pH values. Amylase-periodic acid-Schiff staining was used to visualize capillaries around fibers. ACE-II subjects had significantly (p < 0.01) higher percentages of type I fibers (50.1 +/- 13.9%vs 30.5 +/- 13.3%) and lower percentages of type IIb fibers (16.2 +/- 6.6%vs 32.9 +/- 7.4%) than ACE-DD subjects. The linear trends for decreases in type I fibers and increases in type IIb fibers from ACE-II --> ID --> DD genotypes were significant as assessed by an analysis of variance. The ratio of type I:II fibers also differed according to the ACE genotype. A multivariate logistic regression analysis showed that the ACE-I allele had significant additive and recessive (codominant) effects on the increased type I fibers and the ratio of type I:II fibers. No specific pattern of capillarization was observed among the three ACE genotypes. In conclusion, the ACE-I allele was associated with increased type I SMF, which may be a mechanism for the association between the ACE genotype and endurance performance.

Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension.

We studied the association of angiotensin I-converting enzyme (ACE) gene polymorphism with the depressor response to exercise therapy in 64 Japanese subjects with mild to moderate essential hypertension. Each subject performed 10 weeks of mild (lactate threshold intensity: approximately 50% maximum oxygen consumption) exercise therapy on a bicycle ergometer. Systolic blood pressure (SPB), diastolic blood pressure (DPB), and mean arterial pressure (MAP) were significantly decreased by exercise therapy in subjects with the ACE-II and ID genotypes but not in DD subjects. The time-by-genotype interaction effects were significant for DBP and MAP. According to a multiple logistic regression analysis, the age- and baseline plasma renin activity-adjusted relative risk (odds ratio) for the lack of a depressor response conferred by the D allele (assuming an additive effect) was 2.72 [95% confidence interval (CI), 1.07-6.91; p = 0.034]; for DD genotypes, as compared with the DI and II genotypes (assuming that the D allele is recessive), it was 11.7 (95% CI, 2.25-60.6; p = 0.003). ACE gene I/D polymorphism is associated with the depressor response of essential hypertensives to mild exercise therapy, which suggests that genetic features may underlie, at least in part, the heterogeneity of the depressor response in essential hypertensives to mild exercise therapy.

Effect of mild exercise training on glucose effectiveness in healthy men.

OBJECTIVE: To detect whether mild exercise training improves glucose effectiveness (S(G)), which is the ability of hyperglycemia to promote glucose disposal at basal insulin, in healthy men. RESEARCH DESIGN AND METHODS: Eight healthy men (18-25 years of age) underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before as well as at 16 h and 1 week after the last training session. S(G) and insulin sensitivity (S(I)) were estimated using a minimal-model approach. RESULTS: After the exercise training, VO(2max) and VO(2) at LT increased by 5 and 34%, respectively (P < 0.05). The mild exercise training improves S(G) measured 16 h after the last training session, from 0.018 +/- 0.002 to 0.024 +/- 0.001 min(-1) (P < 0.05). The elevated S(G) after exercise training tends to be maintained regardless of detraining for 1 week (0.023 +/- 0.002 min(-1), P = 0.09). S(I) measured at 16 h after the last training session significantly increased (pre-exercise training, 13.9 +/- 2.2; 16 h, 18.3 +/- 2.4, x10(-5). min(-1). pmol/l(-1), P < 0.05) and still remained elevated 1 week after stopping the training regimen (18.6 +/- 2.2, x10(-5). min(-1). pmol/l(-1), P < 0.05). CONCLUSIONS: Mild exercise training at LT improves S(G) in healthy men with no change in the body composition. Improving not only S(I) but also S(G) through mild exercise training is thus considered to be an effective method for preventing glucose intolerance.

Effect of moderate exercise on immune senescence in men.

The purpose of this study was to examine the relationship between active compared to inactive lifestyles and immunocompetence in men. Subjects, all male volunteers, regularly exercising moderately were separated into three age groups: young (20-39 years), middle-aged (40-59 years) and elderly (more than 60 years). Age-matched sedentary male subjects served as controls in each group. Immunological assessments were, total leucocyte count, lymphocyte subpopulation counts, natural killer cell activity and neutrophilic phagocytosis. Total leucocyte and T-cell (CD3+) counts were not significantly different among the groups. Among T-cell subsets, there was a slight increase in helper T-cell (CD3+CD4+) and a decrease in cytotoxic/suppressor T-cell (CD3+CD8+) concentrations in the older sedentary subjects, resulting in an age-associated significant increase in the CD4:CD8 ratio among those control groups. However, among the exerciser groups, no such increase and decrease in the T-cell subpopulations or an age-related increase of the CD4:CD8 ratio were observed. Considering the components of innate immunity, the concentration of NK-cells (CD16+CD56+) significantly increased in the elderly exercisers, compared to that of the age-matched control subjects, or of the young group. The phagocytotic activity of neutrophils showed an age-associated decline, but of lesser degree in the elderly exercisers than in the elderly controls. Taken together, these results suggest that habitual and moderate training in later life is associated with a lesser age-related decline in certain aspects of circulating T-cell function and innate immunity.

Acute creatine loading enhances human growth hormone secretion.

BACKGROUND: The main objective of this study was to explore the effect of acute creatine (Cr) ingestion on the secretion of human growth hormone (GH). METHODS: In a comparative cross-sectional study, 6 healthy male subjects ingested in resting conditions a single dose of 20 g creatine (Cr-test) vs a control (c-test). During 6 hours the Cr, creatinine and GH concentrations in blood serum were measured after Cr ingestion (Cr-test). RESULTS: During the Cr-test, all subjects showed a significant stimulation of GH (p<0.05), but with a large interindividual variability in the GH response: the difference between Cr-test and c-test averaged 83% (SD 45%). For the majority of subjects the maximum GH concentration occurred between 2 hrs and 6 hrs after the acute Cr ingestion. CONCLUSIONS: In resting conditions and at high dosages Cr enhances GH secretion, mimicking the response of strong exercise which also stimulates GH secretion. Acute body weight gain and strength increase observed after Cr supplementation should consider the indirect anabolic property of Cr.

Influence of mild exercise at the lactate threshold on glucose effectiveness.

The effect of a single bout of mild exercise on glucose effectiveness (S(G)) and insulin sensitivity (S(I)) was studied in six young male subjects by using a minimal model. An intravenous glucose tolerance test was performed under two conditions as follows: 1) 25 min after a bout of exercise on a cycle ergometer at the lactate threshold level for 60 min (Ex) and 2) without any prior exercise (Con). Leg blood flow (LBF) was also measured by strain-gauge plethysmography simultaneously with blood sampling. S(I) did not significantly change after exercise (18.1 +/- 1.5 vs. 17.7 +/- 1.9 x 10-(5) min/pM), whereas S(G) significantly increased (0.016 +/- 0.002 vs. 0.025 +/- 0.002 min(-1), P < 0.01). The increased blood flow after exercise remained high during the time period for measurement of the glucose disappearance constant and may be a determinant of S(G). The incremental lactate area under the curve until insulin loading was also significantly higher in Ex than in Con (2.6 +/- 0.9 vs. -3.5 +/- 1.5 mM/min, P < 0.05). These results suggest that increased S(G) after mild exercise may be due, at least in part, to increased LBF and lactate production under a hyperglycemic state.

Acute creatine ingestion in human: consequences on serum creatine and creatinine concentrations.

The aim of the study was to explore the effect of an acute dose of creatine (Cr) ingestion on serum Cr and serum creatinine (Crn) concentrations. Sixteen healthy subjects ingested a single dose of Cr (20 g) followed by the measurement of serum Cr and Crn concentration for 3 h up to a maximum of 6 h (n=6). In response to Cr ingestion a large rise in serum Cr concentration was observed (by 50 folds) occurring approximately 2 1/2h after the ingestion (peak value of 2.17 +/- 0.66 mmol x l(-1)). We also found a moderate but significant rise in serum Crn concentration averaging 13 % after 3 h (peak value at 99.5 +/- 10.5 micromol x l(-1)). A dose response curve obtained in two case studies, in whom different doses of Cr were ingested (0, 2.5, 5, 10, 15, 20 g and 0, 10, 20, 30 g), showed that serum Cr concentration as well as the peak time increased linearly with Cr ingestion. In addition, acute Crn ingestion (5 g) resulted in a substantial increase in serum Crn concentration (by 10 folds) but led to a minor rise in serum Cr concentration (by 2 folds). These results suggest that when acute doses of Cr are ingested in humans, the degree of conversion of exogenous Cr to Crn in the stomach and the gut can be considered as negligible following the first 6 h of ingestion. However, further studies are required to explore the prolonged effect of Cr on Crn metabolism.

Intravenous glucose tolerance test-derived glucose effectiveness in strength-trained humans.

The effect of long-term strenuous resistance training on glucose effectiveness (SG) was examined by comparing 11 strength-trained and 20 sedentary males by a minimal model approach. Lean body mass (LBM) was measured by hydrostatic weighing. The LBM in strength-trained subjects (65.7 +/- 3.1 kg) was significantly larger than in sedentary subjects (56.6 +/- 1.2 kg, P < .01). The glucose disappearance constant ([KG] 3.07% +/- 0.45% min(-1)) and insulin sensitivity ([SI] 17.5 +/- 2.0 x 10(-5) x min(-1) x pmol/L(-1)) in strength-trained subjects were significantly higher than in sedentary subjects (2.06% +/- 0.14% x min(-1) and 10.3 +/- 1.2 x 10(-5) x min(-1) x pmol/L(-1), P < .05). SG in strength-trained subjects (0.024 +/- 0.003 min(-1)) was significantly higher than in sedentary subjects (0.018 +/- 0.001 min(-1), P < .05). These results thus suggest that the improved glucose tolerance in strength-trained subjects was due to increased SG and SI.

Blood pressure lowering effect of low intensity aerobic training in elderly hypertensive patients.

PURPOSE: The purpose of this investigation was to determine the effect of 9 months of low intensity aerobic training on blood pressure in elderly hypertensive patients who were receiving antihypertensive medication. METHODS: The training group (N = 13; mean age 75.4 +/- 5.4 yr) agreed to take part in physical training using a treadmill with an exercise intensity at the blood lactate threshold (LT) for 30 min three to six times a week for 9 months. The rest (N = 13; mean age 73.1 +/- 4.2 yr) served as controls. RESULTS: The resting systolic (-15 +/- 8 mm Hg), mean (-11 +/- 6 mm Hg), and diastolic blood pressures (-9 +/- 9 mm Hg) decreased significantly after 3 months of training and the blood pressure of all participants stabilized at a significantly lower level by the end of the study (9 months) in the training group, whereas no significant changes in blood pressure were found in the control group. Both the pretraining systolic and diastolic blood pressure of those recruited patients negatively correlated with those changes after the training (SBP: P < 0.01; DBP: P < 0.05, respectively). After 1 month of detraining in five patients, the blood pressure levels were similar to those in the pretraining state. The LT increased significantly in the training group (P < 0.01). CONCLUSION: In conclusion, an additional antihypertensive effect of mild aerobic training at the LT was confirmed in elderly patients receiving antihypertensive medication. The cessation of such training in five patients, however, resulted in a relatively rapid return to pretraining levels within a month.

Double product response is accelerated above the blood lactate threshold.

Catecholamine concentrations are known to increase sharply in the blood at work rates above the blood lactate threshold (LT); thus, we hypothesized that the double product (DP, heart rate-systolic blood pressure product) may also abruptly increase at work rates above the LT. Ninety healthy students performed a stepwise incremental test on a cycle ergometer. The slopes of the two regression lines below and above the LT for the heart rate (HR), the indirectly measured systolic blood pressure (SBP), and the DP, respectively, were compared using VO2 as an independent variable. For all three parameters the slope of the regression line above the LT was significantly higher than that below the LT. Although either the same or a lower slope was found in the HR (N = 23) or SBP (N = 22) responses in some subjects above the LT as compared with that below the LT, a steeper DP slope above the LT was evident in all 90 subjects. The same results were also obtained during 4-min constant work rate exercise sessions at a variety of submaximal intensities performed in a random order in seven subjects. In addition, we established the DP break point (DPBP) determining protocol with a fairly good test-retest reliability (r = 0.951) and a correlation coefficient between the DPBP and the LT (r = 0.900). These results suggest that the DP increases more steeply above the LT, and, as a result, the DPBP is considered to be a valid and useful parameter as a marker of the LT.

Dietary red pepper ingestion increases carbohydrate oxidation at rest and during exercise in runners.

The effects of dietary hot red pepper on energy metabolism at rest and during exercise were examined in long distance male runners 18-23 yr of age. A standardized meal was given on the evening prior to the experiment. The subjects had a meal (2720 kJ) with or without 10 g of hot red pepper for breakfast. During rest (2.5 h after meal) and exercise (pedaling for 1 h at 150 W, about 60% VO2max, using cycling ergometry), expired gasses and venous blood were collected. The meal with hot red pepper significantly elevated respiratory quotient and blood lactate levels at rest and during exercise. Oxygen consumption at rest was slightly but nonsignificantly higher in the hot red pepper meal at 30 min after the meal. Plasma epinephrine and norepinephrine levels were significantly higher in those who had only hot red pepper at 30 min after the meal. These results suggest that hot red pepper ingestion stimulates carbohydrate oxidation at rest and during exercise.

Identification of the anaerobic threshold using double product in patients with coronary artery disease.

This study compared the ventilatory threshold with the double-product break point in 104 patients with cardiovascular disease during ramp treadmill testing. The high correlation (r = 0.81) between the double-product break point and the ventilatory threshold, even in patients taking beta blockers, suggests the former method is a viable noninvasive alternative for identifying the anaerobic threshold in patients with cardiovascular disease, particularly when expired gas analysis is not appropriate or available.

Effects of a single bout of exercise on glucose effectiveness.

The effects of a single bout of exercise on glucose effectiveness (SG) and insulin sensitivity (SI) in 22 sedentary subjects were estimated with a minimal model approach. The intravenous glucose tolerance test (IVGTT) was performed 1) 11 h after an exercise bout on a cycle ergometer at the lactate threshold level (mild exercise) for 60 min, 2) 11 h after an exercise bout at the 4 mM lactate level (hard exercise) for 36 +/- 1 min, 3) 11 h after an exhaustive-exercise bout (exhaustive exercise) for 96 +/- 7 min, or 4) without any prior exercise (control). Only the exhaustive exercise increased the glucose disappearance constant (2.69 +/- 0.28 vs. 2.05 +/- 0.13%/min; P < 0.05) and SI (15.0 +/- 2.0 vs. 10.3 +/- 0.9 x 10(-5) min/pM: P < 0.05) in comparison with the control condition. The SG and SG at zero insulin (GEZI) were not affected by any exercise condition. However, a marked individual difference in GEZI emerged after the exhaustive exercise and could be divided into two subgroups: one decreased in GEZI (0.014 +/- 0.001 vs. 0.007 +/- 0.001 min-1) and the other increased in GEZI (0.014 +/- 0.001 vs. 0.021 +/- 0.003 min-1). The former subgroup was accompanied by elevated levels of plasma creatine kinase (100 +/- 16 vs. 598 +/- 315 IU/l; P < 0.05) and myoglobin (Mb; 46 +/- 4 vs. 126 +/- 47 ng/ml; P < 0.05), whereas the latter subgroup showed no significant change in creatinine kinase (99 +/- 10 vs. 128 +/- 9 IU/l; P > 0.05) and Mb (50 +/- 7 vs. 51 +/- 4 ng/ml; P > 0.05). In both subgroups, SI was similarly increased after the exhaustive exercise. These results thus suggest that a single bout of exercise that results in muscle damage or changes in muscle permeability, as reflected in the increased creatine kinase and Mb levels, decreases GEZI, whereas exhaustive exercise without such alterations increases GEZI.

Impaired non-insulin mediated glucose uptake after downhill running in rats.

To evaluate the effects of a single bout of exercise on non-insulin mediated glucose uptake in rats, hyperglycemic clamp tests were performed either 12 h after the rats were subjected to downhill running (90 min, -16 degrees incline, n = 10) or without any prior exercise (n = 10). Somatostatin (1.0 microgram/kg/min) was infused during clamps to suppress insulin secretion, while the serum glucose was clamped at a level of 200 mg/dl for 100 min. The serum insulin levels during the hyperglycemic clamp was maintained at basal levels. The non-insulin mediated glucose disposal rate was significantly decreased during clamp performed after downhill running (5.45 +/- 0.61 mg/kg/min) compared to the control conditions (9.63 +/- 0.32 mg/kg/min, P < 0.01). The creatine kinase level after downhill running (561 +/- 206 IU/l) was significantly higher than the control conditions (118 +/- 20 IU/l, P < 0.01). These results thus suggest that the muscle damage caused by downhill exercise, which predominantly consists of eccentric type, may therefore decrease the non-insulin mediated glucose uptake.

Effects of red-pepper diet on the energy metabolism in men.

We investigated the effects of dietary red pepper on the energy metabolism in male subjects. In the first experiment, after having a standardized dinner on the previous evening, the subjects consumed a breakfast (650 kcal) either with or without 10 g of red pepper. For 150 min after the meal, they took a rest and their expired gas was collected. During the initial 30 min after the meal, the energy expenditure tended to be higher in the red-pepper diet period than in the control diet period. For the remaining 120 min, no difference in the energy expenditure was found between the red-pepper diet period and the control diet period. However the carbohydrate oxidation was significantly higher in the red-pepper diet period than in the control diet period while the lipid oxidation was lower in the red-pepper diet period than in the control diet period for 150 min after the meal. In the second experiment, the subjects consumed a breakfast with 10 g of red pepper after an oral administration of propranolol or a placebo. The propranolol abolished the increase in energy expenditure during the initial 30 min due to the meal containing red pepper. For the remaining 120 min, no difference in energy expenditure was found between the propranolol period and the placebo period. These results suggest than an increase in the energy expenditure after the meal containing red pepper appeared only immediately after the meal ingestion and a red-pepper diet increases the carbohydrate oxidation without increasing total energy expenditure for 150 min after the meal. And an increase in the energy expenditure immediately after the meal containing red pepper is considered to be caused by beta-adrenergic stimulation.

Activation of renal dopamine system by physical exercise.

Physical exercise is one of the life-style modifications used for lowering blood pressure. Except for diminished norepinephrine spill over, the mechanism by which physical exercise exerts its effects was not known. Based on our preliminary finding that the reduction of blood pressure was inversely correlated to the baseline plasma renin activity, we have consequently revealed that mild exercise reduces plasma volume and hence the cardiac index. In order to elucidate the mechanism, we have investigated all possible parameters relevant to plasma volume regulation. Among them, urinary free dopamine and urinary active kallikrein increased in the early stages (weeks 2-4) while atrio-natriuretic factor (week 4) and endogeneous ouabain-like substance (EOLS) consequently (weeks 7-10) decreased. Serum taurine increased and plasma norepinephrine decreased in the late stages. The conclusion reached is that mild exercise seems to first activate the renal dopamine and kallikrein systems and second trigger other mechanism, such as an increase in taurine and decreases in EOLS and norepinephrine.