Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men.

INTRODUCTION/PURPOSE: Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 ± 4 yr; V˙O2max, 48 ± 2 mL·kg·min) after repeated prolonged exercise). METHODS: A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. V˙O2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. RESULTS: The daily duration of exercise was 10 h and 31 ± 37 min, and the mean intensity was 53% ± 1% of V˙O2max. Body weight remained unchanged. V˙O2max and maximal fat oxidation rate decreased by 6% ± 2% (P = 0.04) and 32% ± 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 ± 77 µmol·L to 160 ± 38 µmol·L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and ß-hydroxy-acyl-CoA-dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. CONCLUSIONS: Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise.

Blood temperature and perfusion to exercising and non-exercising human limbs.

NEW FINDINGS: What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (TB ), blood flow and oxygen uptake (V̇O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher TB and limb V̇O2. Leg and arm vascular conductance during exercise compared with rest was related closely to TB (r(2) = 0.91; P < 0.05), plasma ATP (r(2) = 0.94; P < 0.05) and limb V̇O2 (r(2) = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in TB and limb V̇O2, whereas ABF, arm TB and V̇O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V̇O2. In 12 trained males, increases in femoral TB and LBF during incremental leg exercise were mirrored by similar pulmonary artery TB and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, TB and aerobic metabolism in exercising and non-exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V̇O2 contribute to the regulation of limb perfusion through control of intravascular ATP.

Ethnic differences in leptin and adiponectin levels between Greenlandic Inuit and Danish children.

OBJECTIVE: In a recent study, we found that Greenlandic Inuit children had a more adverse metabolic profile than Danish children. Aerobic fitness and adiposity could only partly account for the differences. Therefore, we set out to evaluate and compare plasma leptin and adiponectin levels in Danish and Inuit children. METHODS: In total, 187 Inuit and 132 Danish children (5.7-17.1 years) had examinations of anthropometrics, body fat content, pubertal staging, fasting blood and aerobic fitness. RESULTS: Plasma leptin was higher in Danish boys [3,774 (4,741-3,005)] [pg/mL unadjusted geometric mean (95% CI)] compared to both northern [2,076 (2,525-1,706)] (p < 0.001) and southern (2,515 (3,137-2,016)) (p < 0.001) living Inuit boys and higher in Danish girls [6,988 (8,353-5,847)] compared to southern living Inuit girls [4,910 (6,370-3,785)] (p = 0.021) and tended to be higher compared to northern living Inuit girls [5,131 (6,444-4,085)] (p = 0.052). Plasma adiponectin was higher for both Danish boys [22,359 (2,573-19,428)] [ng/mL unadjusted geometric mean (95% CI)] and girls [26,609 (28,994-24,420)] compared to southern living Inuit boys [15,306 (18,406-12,728)] and girls [18,864 (22,640-15,717)] (both p < 0.001), respectively. All differences remained after adjustment for body fat percentage (BF%), aerobic fitness, age and puberty. The leptin/adiponectin ratio was higher in Danish boys and tended to be higher in Danish girls compared to northern living Inuit boys and girls, respectively. These differences were eliminated after adjustment for BF%, aerobic fitness, age and puberty. CONCLUSIONS: In contrast to our hypothesis, plasma leptin was higher in Danish children despite a more healthy metabolic profile compared to Inuit children. As expected, plasma adiponectin was lowest in Inuit children with the most adverse metabolic profile.

Metabolic profile in two physically active Inuit groups consuming either a western or a traditional Inuit diet.

OBJECTIVES: To evaluate the effect of regular physical activity on metabolic risk factors and blood pressure in Inuit with high BMI consuming a western diet (high amount of saturated fatty acids and carbohydrates with a high glycemic index). STUDY DESIGN: Cross sectional study, comparing Inuit eating a western diet with Inuit eating a traditional diet. METHODS: Two physically active Greenland Inuit groups consuming different diet, 20 eating a traditional diet (Qaanaaq) and 15 eating a western diet (TAB), age (mean (range)); 38, (22-58) yrs, BMI; 28 (20-40) were subjected to an oral glucose tolerance test (OGTT), blood sampling, maximal oxygen uptake test, food interview/collection and monitoring of physical activity. RESULTS: All Inuit had a normal OGTT. Fasting glucose (mmol/l), HbA1c (%), total cholesterol (mmol/l) and HDL-C (mmol/l) were for Qaanaaq women: 4.8±0.2, 5.3±0.1, 4.96±0.42, 1.34±0.06, for Qaanaaq men: 4.9±0.1, 5.7±0.1, 5.08±0.31, 1.28±0.09, for TAB women: 5.1±0.2, 5.3±0.1, 6.22±0.39, 1.86±0.13, for TAB men: 5.1±0.2, 5.3±0.1, 6.23±0.15, 1.60±0.10. No differences were found in systolic or diastolic blood pressure between the groups. There was a more adverse distribution of small dense LDL-C particles and higher total cholesterol and HDL-C concentration in the western diet group. CONCLUSIONS: Diabetes or impaired glucose tolerance was not found in the Inuit consuming either the western or the traditional diet, and this could, at least partly, be due to the high amount of regular daily physical activity. However, when considering the total cardio vascular risk profile the Inuit consuming a western diet had a less healthy profile than the Inuit consuming a traditional diet.

Erythropoietin down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate in humans.

Recombinant human erythropoietin (rHuEPO) elevates haemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin­aldosterone system and renal function. Sixteen healthy males were given rHuEPO for 28 days in doses raising the haematocrit to 48.3±4.1%.Renal clearance studieswith urine collections (N = 8) were done at baseline and at days 4, 11, 29 and 42. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA.Renal clearance of lithium (CLi)was used as an index of proximal tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in haematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO decreased plasma levels of renin and aldosterone (N = 8) by 21­33% (P < 0.05) and 15­36% (P < 0.05), respectively. After cessation of rHuEPO, values returned to baseline. On days 11 and 29, CLi increased (P < 0.02) indicating a significant 10­16% decrease in absolute proximal reabsorption of sodium and water (APR = GFR − CLi, P < 0.05). GFR decreased slightly, albeit significantly, on day 4 (P < 0.05). In conclusion, rHuEPO promptly, and before any changes in blood volumes and haematocrit can be detected, causes a down-regulation of the renin­aldosterone system. The results are compatible with a rHuEPO-induced reduction in proximal reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in GFR. Therefore, treatment with rHuEPO may result in suppression of endogenous EPO synthesis secondary to a decrease in intrarenal oxygen consumption.

Screening for recombinant human erythropoietin using [Hb], reticulocytes, the OFF(hr score), OFF(z score) and Hb(z score): status of the Blood Passport.

Haemoglobin concentration ([Hb]), reticulocyte percentage (retic%) and OFF(hr score) are well-implemented screening tools to determine potential recombinant human erythropoietin (rHuEpo) abuse in athletes. Recently, the International Cycling Union implemented the OFF(z score) and the Hb(z score) in their anti-doping testing programme. The aim of this study is to evaluate the sensitivity of these indirect screening methods. Twenty-four human subjects divided into three groups with eight subjects each (G1; G2 and G3) were injected with rHuEpo. G1 and G2 received rHuEpo for a 4-week period with 2 weeks of "boosting" followed by 2 weeks of "maintenance" and a wash-out period of 3 weeks. G3 received rHuEpo for a 10-week period (boost = 3 weeks; maintenance = 7 weeks; wash out = 1 week). Three, seven and eight of the 24 volunteers exceeded the cut-off limits for OFF(hr score), [Hb] and retic%, respectively. One subject from G1, nobody from G2, and seven subjects from G3 exceeded the cut-off limit for Hb(z score.) In total, ten subjects exceeded the cut-off limit for the OFF(z score); two subjects from G1, two subjects from G2 and six subjects from G3. In total, indirect screening methods were able to indicate rHuEpo injections in 58% of subjects. However, 42% of our rHuEpo-injected subjects were not detected. It should be emphasised that the test frequency in real world anti-doping is far less than the present study, and hence the detection rate will be lower.

Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty.

CONTEXT: The GH/IGF-I axis has major impact on insulin sensitivity and insulin secretion. Recently a polymorphism in the GH receptor gene (GHR), a genomic deletion of exon 3 (GHRd3), has been linked to increased responsiveness to GH. OBJECTIVE: The objective of the present study was to evaluate the impact of the GHRd3 gene polymorphism on insulin sensitivity, insulin secretion, lipids, and IGF-I levels in healthy children and adolescents. DESIGN: This was cross-sectional and was part of the COPENHAGEN puberty study. SETTING: The study was conducted at a tertiary center for pediatric endocrinology. PARTICIPANTS: Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5-16.1 yr. INTERVENTIONS: Standard 2-h oral glucose tolerance tests were preformed. GHR genotypes were determined by multiplex PCR. Main outcome measures were insulin sensitivity, insulin secretion, serum lipids, and IGF-I levels. RESULTS: Insulin secretion was higher in children and adolescents with a least one GHRd3 allele, even after adjustment for age, sex, pubertal stage, and insulin sensitivity (P = 0.018). Disposition index was higher in GHRd3-positive subjects (P = 0.026). In addition, the GHRd3 allele was associated with higher triglyceride (P = 0.028), but not IGF-I levels. CONCLUSION: The presence of at least one GHRd3 allele was associated with higher insulin secretion for a given degree of insulin sensitivity in healthy children and adolescents during puberty. In addition, the presence of the GHRd3 allele was associated with a higher disposition index. Thus, this common polymorphism in the GHR gene might play a role for pancreatic beta-cell compensatory capacity.

Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty.

OBJECTIVE: Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor of glucose metabolism and metabolic risk during puberty. RESEARCH DESIGN AND METHODS: This was a cross-sectional study on 132 healthy Caucasian children and adolescents evaluated by an oral glucose tolerance test, a dual-energy X-ray absorptiometry scan, direct oxygen uptake measurement during cycle ergometry, and fasting blood samples. RESULTS: SHBG levels declined with advancement of puberty in both boys (P < 0.001) and girls (P = 0.019). SHBG was significantly positively associated with insulin sensitivity in boys (P < 0.001) and girls (P < 0.001). In addition, SHBG was a strong predictor of insulin sensitivity (P = 0.001) and the only predictor of the disposition index (P = 0.031) after adjustment for puberty, fat mass, and aerobic fitness. SHBG was significantly negatively associated with metabolic risk (P = 0.032) and with hypersensitive C-reactive protein levels (P = 0.030) after adjustment for relevant confounders. CONCLUSIONS: SHBG was a strong predictor of insulin sensitivity and metabolic risk during puberty. Thus, we hypothesize that SHBG integrates the marked changes in glucose metabolism and body composition that occur during the pubertal transition.

Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer.

To determine central and peripheral hemodynamic responses to upright leg cycling exercise, nine physically active men underwent measurements of arterial blood pressure and gases, as well as femoral and subclavian vein blood flows and gases during incremental exercise to exhaustion (Wmax). Cardiac output (CO) and leg blood flow (BF) increased in parallel with exercise intensity. In contrast, arm BF remained at 0.8 l/min during submaximal exercise, increasing to 1.2 +/- 0.2 l/min at maximal exercise (P < 0.05) when arm O(2) extraction reached 73 +/- 3%. The leg received a greater percentage of the CO with exercise intensity, reaching a value close to 70% at 64% of Wmax, which was maintained until exhaustion. The percentage of CO perfusing the trunk decreased with exercise intensity to 21% at Wmax, i.e., to approximately 5.5 l/min. For a given local Vo(2), leg vascular conductance (VC) was five- to sixfold higher than arm VC, despite marked hemoglobin deoxygenation in the subclavian vein. At peak exercise, arm VC was not significantly different than at rest. Leg Vo(2) represented approximately 84% of the whole body Vo(2) at intensities ranging from 38 to 100% of Wmax. Arm Vo(2) contributed between 7 and 10% to the whole body Vo(2). From 20 to 100% of Wmax, the trunk Vo(2) (including the gluteus muscles) represented between 14 and 15% of the whole body Vo(2). In summary, vasoconstrictor signals efficiently oppose the vasodilatory metabolites in the arms, suggesting that during whole body exercise in the upright position blood flow is differentially regulated in the upper and lower extremities.