Exercise attenuates nuclear protein binding to gene regulatory sequences of hepatic fatty acid synthase.
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The effect of an acute bout of exhaustive exercise on hepatic fatty acid synthase (FAS) gene expression was examined in rats. Female Sprague-Dawley rats (age 8 wk) were fasted for 48 h (F, n = 6), or fasted, refed a high-fructose diet for 6 h, and killed at rest (R, n = 6) or killed after running on a treadmill at 27 m/min and 5% grade for 88 +/- 7 min (E, n = 6). Gel mobility shift assay indicated that R rats had twofold higher liver nuclear protein binding to oligonucleotides corresponding to the insulin responsive sequence (-71/-50) and carbohydrate response element (+283/+303) on the FAS promoter, compared with F rats. Exercise severely attenuated this binding in liver nuclear extracts to the levels seen in F rats. Competition and supershift experiments revealed that the bound protein complexes contained the upstream stimulatory factors. Nuclear run-on experiment revealed a 49-fold increase in transcription rate of the FAS gene in R vs. F rats, whereas exercise suppressed the transcription rate. FAS mRNA abundance and FAS enzyme activity were dramatically increased with refeeding but were unaltered by exercise. The results reveal that dietary induction of hepatic FAS is stimulated by increased nuclear protein binding to insulin responsive sequence and carbohydrate response element, whereas exhaustive exercise attenuates the binding, which may precede downregulation of FAS mRNA and enzyme synthesis reported in our previous work (M. A. Griffiths, R. Fiebig, M. T. Gore, D. H. Baker, K. Esser, L. Oscai, and L. L. Ji. J. Nutr. 126, 1959-1971, 1996). (+info)
Effect of carotid body denervation on breathing in neonatal goats.
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The objective of the present study was to determine in goats whether carotid body denervation (CBD) at 1-3 days of age causes permanent changes in breathing greater than those that occur after CBD in adult goats. Goats underwent CBD (n = 6) or sham CBD (n = 3) surgery at 1-3 days of age. In addition, one unoperated control animal was studied. Bolus intravenous injections of NaCN 2 days postsurgery verified successful CBD surgery. However, at 3, 11, and 18 mo of age, the CBD goats had regained a NaCN response that did not differ (P > 0.10) from that of intact goats. Intracarotid NaCN injections elicited a hyperpnea in the sham CBD but not the CBD goats. Only one animal exhibited highly irregular breathing [characterized by prolonged (>9-s) apneas] after CBD, and the irregularity disappeared by 3 mo of age. One CBD goat died at 35 days of age, and autopsy revealed that death was associated with pneumonia. After 3 mo of age, there were no statistically significant differences (P > 0.10) between sham and CBD goats in eupneic breathing, hypoxia and CO(2) sensitivity, and the exercise hyperpnea. It is, therefore, concluded that CBD at 1-3 days of age in goats does not appear to affect selected aspects of respiratory control after 3 mo of age, conceivably because of the emergence of other functional chemoreceptors that compensate for the loss of the carotid chemoreceptor. (+info)
Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exercise.
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This study had the following objectives: 1) to determine whether diabetic rats could increase muscle mass due to a physiological manipulation (chronic resistance exercise), 2) to determine whether exercise training status modifies the effect of the last bout of exercise on elevations in rates of protein synthesis, and 3) to determine whether chronic resistance exercise alters basal glycemia. Groups consisted of diabetic or nondiabetic rats that performed progressive resistance exercise for 8 wk, performed acute resistance exercise, or remained sedentary. Arterial plasma insulin in diabetic groups was reduced by about one-half (P < 0.05) compared with nondiabetic groups. Soleus and gastrocnemius-plantaris complex muscle wet weights were lower because of diabetes, but in response to chronic exercise these muscles hypertrophied in diabetic (0.028 +/- 0.003 vs. 0.032 +/- 0.0015 g/cm for sedentary vs. exercised soleus and 0.42 +/- 0.068 vs. 0.53 +/- 0.041 g/cm for sedentary vs. exercised gastrocnemius-plantaris, both P < 0.05) but not in nondiabetic (0.041 +/- 0.0026 vs. 0.042 +/- 0.003 g/cm for sedentary vs. exercised soleus and 0.72 +/- 0.015 vs. 0.69 +/- 0.013 g/cm for sedentary vs. exercised gastrocnemius-plantaris) rats when muscle weight was expressed relative to tibial length or body weight (data not shown). Another group of diabetic rats that lifted heavier weights showed muscle hypertrophy. Rates of protein synthesis were higher in red gastrocnemius in chronically exercised than in sedentary rats: 155 +/- 11 and 170 +/- 7 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in exercised diabetic and nondiabetic rats vs. 110 +/- 14 and 143 +/- 7 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in sedentary diabetic and nondiabetic rats. These elevations, however, were lower than in acutely exercised (but untrained) rats: 176 +/- 15 and 193 +/- 8 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in diabetic and nondiabetic rats. Finally, chronic exercise training in diabetic rats was associated with reductions in basal glycemia, and such reductions did not occur in sedentary diabetic groups. These data demonstrate that, despite lower circulating insulin concentrations, diabetic rats can increase muscle mass in response to a physiological stimulus. (+info)
Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing.
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The purpose of the present study was to determine whether it is possible to alter the development of fatigue and ablate free radical-mediated lipid peroxidation of the diaphragm during loaded breathing by administering oxypurinol, a xanthine oxidase inhibitor. We studied 1) room-air-breathing decerebrate, unanesthetized rats given either saline or oxypurinol (50 mg/kg) and loaded with a large inspiratory resistance until airway pressure had fallen by 50% and 2) unloaded saline- and oxypurinol-treated room-air-breathing control animals. Additional sets of studies were performed with animals breathing 100% oxygen. Animals were killed at the conclusion of loading, and diaphragmatic samples were obtained for determination of thiobarbituric acid-reactive substances and assessment of in vitro force generation. We found that loading of saline-treated animals resulted in significant diaphragmatic fatigue and thiobarbituric acid-reactive substances formation (P < 0.01). Oxypurinol administration, however, failed to increase load trial time, reduce fatigue development, or prevent lipid peroxidation in either room-air-breathing or oxygen-breathing animals. These data suggest that xanthine oxidase-dependent pathways do not generate physiologically significant levels of free radicals during the type of inspiratory resistive loading examined in this study. (+info)
Endothelin-1 sensitivity of porcine coronary arteries is reduced by exercise training and is gender dependent.
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We tested the hypothesis that exercise training reduces the sensitivity of coronary smooth muscle to endothelin-1 (ET-1), with the adaptation being greater in male than in female miniature swine. The efficacy of training was similar in males and females. Cumulative ET-1 contractile responses of coronary branches and left circumflex artery were significantly shifted to the right in exercise-trained (Ex) males but not in Ex females. Analyses of the excitatory concentration causing a 50% response (EC(50)) showed a 1.7- to 2.2-fold shift in Ex males with no change in maximum tension. Nonselective blockade of K-channel activity with tetraethylammonium (TEA; 30-50 mM) significantly shifted the EC(50) to a lower concentration in both Ex males (1.25-fold) and Ex females (2.2-fold) but not in sedentary (Sed) groups. Females (combined Sed and Ex) exhibited a greater response to TEA than did combined Sed and Ex males. Changes in [(32)P]phosphatidic acid ([(32)P]PA) provided an indicator of ET-1-induced phospholipase activity. The magnitude of the [(32)P]PA response was reduced by Ex in both males and females without affecting the EC(50). It is concluded that the contractile sensitivity of coronary arteries to ET-1 is influenced by physical activity in a gender-dependent manner. It is unclear why the contractile sensitivity in females was not reduced by Ex as in the males, because Ex significantly affected responses to TEA and ET-1 stimulation of [(32)P]PA production in both males and females. A potential gender difference in K-channel function may contribute to this discrepancy. (+info)
In vivo evidence that endogenous dopamine modulates sympathetic activity in man.
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Dopamine receptors type 2 (D2)-like receptor blockers cause an increase in the norepinephrine response to intense physical exercise. However, during intense physical exercise, D2-like antagonists also cause an increase in the epinephrine response, which itself might cause an increase in plasma norepinephrine through the activation of beta2 presynaptic receptors. Therefore, we evaluated the effect of domperidone, a D2-like antagonist, on the norepinephrine response to physical exercise in 6 Addison patients (3 were adrenalectomized and 3 had adrenal tuberculosis). In these patients, the norepinephrine increase observed during exercise was significantly higher after the administration of domperidone than a placebo (F=4,328; P<0.001). Because peripheral plasma norepinephrine does not reflect the sympathetic tone to the heart accurately, we evaluated the effect of domperidone administration (20 mg orally) on the sympathovagal balance, which was measured by the ratio between the high- and low-frequency components of heart rate variability, in 9 normal volunteers in the supine and sitting positions. When compared with placebo, domperidone caused a significant increase in the low/high frequency ratio (P<0.05) in the sitting position without modifying basal and stimulated norepinephrine plasma levels or blood pressure. These data support a role for endogenous dopamine in modulating norepinephrine release by human sympathetic nerves in vivo. (+info)
Responses to constant work exercise in patients with chronic heart failure.
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OBJECTIVE: To describe the kinetics of metabolic gas exchange at the onset and offset of low level, constant work exercise in patients with chronic heart failure. SETTING: Tertiary referral centre for cardiology. PATIENTS: 10 patients with chronic heart failure and 10 age matched controls. METHODS: Each subject undertook maximum incremental exercise testing with metabolic gas exchange measurements, and a fixed load exercise test at 25 watts with metabolic gas exchange measurements before, during, and after the test. A monoexponential curve was fitted to the data to describe the kinetics of gas exchange at onset and offset of fixed load exercise. OUTCOME MEASURES: Peak oxygen consumption; time constants of onset and offset for metabolic gas exchange variables during constant load exercise. RESULTS: Peak oxygen consumption (mean (SD)) was higher in controls (26.1 (4.3) v 15.3 (5.3) ml/kg/min; p < 0.001) than in heart failure patients. Oxygen consumption during steady state was the same in both groups (9.2 (1.8) ml/kg/min in controls v 8.6 (1.6) in patients). The time constant of onset was the same in each group, but the time constant of offset was longer in patients (1.29 (0.14) v 0.82 (0.07); p < 0.005). There was a relation between peak oxygen consumption and time constant of offset (R = 0.56; p < 0.001). CONCLUSIONS: The dynamics of gas exchange at the onset of low level exercise are normal in heart failure, but the recovery is delayed. The delay is related to the reduction in exercise capacity. A patient may spend a greater portion of the day recovering from exercise, and may not begin the next bout from a position of true recovery, perhaps contributing to the sensation of fatigue. (+info)
Relation between changes in serum hypoxanthine levels by exercise and daily physical activity in the elderly.
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Effect of exercise at mild intensity on the serum levels of hypoxanthine was studied in eleven healthy elderly subjects. They were divided into the active and sedentary groups according to their daily physical activity. They performed exercise testing to walk for 5 minutes keeping heart rate at approximately 70% of the maximum heart rate. Mean intensity of exercise estimated according to Karvonen's formula in the active or sedentary group was 41.8 +/- 9.6% or 34.1 +/- 6.1%, respectively. In the sedentary group, the serum hypoxanthine levels at 10 minutes after completion of walk load was significantly higher than that before exercise. Changes in the serum hypoxanthine levels in the active and sedentary groups were -0.97 +/- 1.36 and 0.80 +/- 0.57 micromol/liter, respectively (p < 0.05). This result suggests that mild intensity exercise increases the serum hypoxanthine concentration in the elderly leading inactive daily life, and physical activity suppresses an increase in the serum hypoxanthine levels by mild exercise. (+info)