Sedentary Humans Research Articles

Exercise Prevents Fructose-Induced Hypertriglyceridemia in Healthy Young Subjects

Excess fructose intake causes hypertriglyceridemia and hepatic insulin resistance in sedentary humans. Since exercise improves insulin sensitivity in insulin-resistant patients, we hypothesized that it would also prevent fructose-induced hypertriglyceridemia. This study was therefore designed to evaluate the effects of exercise on circulating lipids in healthy subjects fed a weight-maintenance, high-fructose diet. Eight healthy males were studied on three occasions after 4 days of 1) a diet low in fructose and no exercise (C), 2) a diet with 30% fructose and no exercise (HFr), or 3) a diet with 30% fructose and moderate aerobic exercise (HFrEx). On all three occasions, a 9-h oral [13C]-labeled fructose loading test was performed on the fifth day to measure [13C]palmitate in triglyceride-rich lipoprotein (TRL)-triglycerides (TG). Compared with C, HFr significantly increased fasting glucose, total TG, TRL-TG concentrations, and apolipoprotein (apo)B48 concentrations as well as postfructose glucose, total TG, TRL-TG, and [13C]palmitate in TRL-TG. HFrEx completely normalized fasting and postfructose TG, TRL-TG, and [13C]palmitate concentration in TRL-TG and apoB48 concentrations. In addition, it increased lipid oxidation and plasma nonesterified fatty acid concentrations compared with HFr. These data indicate that exercise prevents the dyslipidemia induced by high fructose intake independently of energy balance.

Does Endurance Training Protect From Lipotoxicity?

Modest regular exercise and reduction of dietary fat halves the risk of developing type 2 diabetes. In overt type 2 diabetes, higher levels of exercise training improve glycemic control, whereas the impact of diet and optimal dietary composition are presently unknown (1). Thus, one can assume that intensive exercise protects from diet-induced insulin resistance. Intravenous lipid infusion is an established model to increase plasma free fatty acids (FFAs) and induce insulin resistance (2,3). Although plasma FFAs and intramyocellular lipid (IMCL) inversely correlate with insulin sensitivity in sedentary humans, athletes store more IMCL despite greater insulin sensitivity. This has been termed the “athletes’ paradox” (4). In this issue of Diabetes , Phielix et al. (5) hypothesize that, relative to their untrained counterparts, the high oxidative capacity of endurance-trained athletes attenuates lipid-induced insulin resistance during hyperinsulinemic-normoglycemic clamp tests. Results showed that the athletes’ higher Vo2max was associated with greater ex vivo muscle mitochondrial capacity, insulin sensitivity, and carbohydrate oxidation. Lipid infusion reduced glucose disposal by 63% in untrained individuals, thereby confirming previous reports (3), but only by 29% in the athletes. The authors explained the athletes’ reduction in glucose disposal exclusively by diminished carbohydrate oxidation. They interpret the concomitant dephosphorylation of muscle glycogen synthase as stimulation of glycogen synthesis reflecting shuttling of glucose into nonoxidative storage as glycogen, in line with the “substrate (glucose:FFA) competition” theory of Randle et al. (6) (Fig. 1). The strength of this article includes combining in vivo and in vitro methods to assess muscle metabolism and signaling without interference from acute exercise effects. Nonetheless, some limitations need to be considered: 1 ) the nominally higher body weight and …

Acute Free Fatty Acid Elevation Eliminates Endurance Training Effect on Insulin Sensitivity

Both training and normal body mass index are associated with high insulin sensitivity, but the mechanism may be different. The aim of the study was to examine whether lean trained humans may be protected from acute free fatty acid (FFA)-induced insulin resistance compared with lean sedentary humans. We conducted an interventional trial using either a 6-h lipid (20% Intralipid at 90 ml/h) or glycerol (2.25 g/100 ml at 90 ml/h) infusion along with a concurrent hyperinsulinemic-euglycemic clamp and serial muscle biopsies (0, 120, 360 min) at a clinical research unit at the University of Minnesota. The study included lean endurance-trained (n = 14) and sedentary (n = 14) individuals matched for age, gender, and body mass index. We measured the decline in glucose infusion rate (GIR) during the hyperinsulinemic-euglycemic clamp. The trained group had higher baseline mitochondrial DNA copy number, mRNA of cytochrome C oxidase subunit 3, and insulin sensitivity (as measured by GIR) compared with the sedentary group. When FFA was acutely elevated to the upper physiological range (0.6-0.7 mEq/liter) by lipid infusion, the GIR in both activity groups declined similarly compared with their respective glycerol controls, although insulin signaling, as measured by Ser 473 pAKT/AKT, remained comparable. Specific to the trained group, the stimulatory effect of hyperinsulinemia on mitochondrial mRNA levels during the glycerol infusion was absent during the lipid infusion. Elevated FFA had similar effects in reducing insulin sensitivity in trained and sedentary humans. In trained participants, this decline was associated with alterations in the skeletal muscle mitochondrial mRNA response to hyperinsulinemia.

Exercise Prevents Fructose‐Induced Hypertriglyceridemia in Healthy Young Males

A high fructose intake increases plasma triglyceride (TG) concentrations in sedentary humans, but the effects of exercise are not known. This study was designed to evaluate the effects of a weight‐maintenance, high fructose diet with or without moderate physical activity.8 healthy males were studied on three occasions, after 4 days on a) a diet low in fructose and no exercise (Ctrl), b) a diet with 30% fructose and no exercise (Fru), or c) a diet with 30% fructose and moderate exercise (60 min cycling at 125 W; FruEx). In each condition, energy intake was adjusted to energy requirements (resting energy requirements times 1.5 for Ctrl and Fru, times 1.7 for FruEx). On each occasion, substrate oxidation was measured by calorimetry and de novo lipogenesis was assessed from VLDL 13C‐palmitate after 13C‐fructose loading.Fru significantly increased TG by 18 ± 12%, and VLDL 13C‐palmitate by 333 ± 231% (both p<0.05 vs Ctrl). FruEx blunted the increase in TG (−6 ± 9%), VLDL 13C‐palmitate (−55 ± 28%), and increased lipid oxidation, non‐esterified fatty acid and beta‐hydroxybutyric acid concentrations by 122 ± 45%, 34 ± 16%, and 48 ± 17 % (all p<0.05 vs Ctrl).We conclude that a moderate exercise prevents fructose‐induced dyslipidemia in healthy males, independently of energy balance. This work was supported by the Swiss National Science Foundation

Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans

Healthy, but sedentary ageing leads to marked atrophy and stiffening of the heart, with substantially reduced cardiac compliance; but the time course of when this process occurs during normal ageing is unknown. Seventy healthy sedentary subjects (39 female; 21–77 years) were recruited from the Dallas Heart Study, a population-based, random community sample and enriched by a second random sample from employees of Texas Health Resources. Subjects were highly screened for co-morbidities and stratified into four groups according to age: G(21−34): 21–34 years, G(35−49): 35–49 years, G5(0−64): 50–64 years, G(≥65): ≥65 years. All subjects underwent invasive haemodynamic measurements with right heart catheterization to define Starling and left ventricular (LV) pressure–volume curves. LV end-diastolic volumes (EDV) were measured by echocardiography at baseline, −15 and −30 mmHg lower-body negative pressure, and 15 and 30 ml kg(−1) saline infusion with simultaneous measurements of pulmonary capillary wedge pressure. There were no differences in heart rate or blood pressures among the four groups at baseline. Baseline EDV index was smaller in G(≥65) than other groups. LV diastolic pressure–volume curves confirmed a substantially greater LV compliance in G(21−34) compared with G(50−64) and G(≥65), resulting in greater LV volume changes with preload manipulations. Although LV chamber compliance in G(50−64) and G(≥65) appeared identical, pressure–volume curves were shifted leftward, toward a decreased distensibility, with increasing age. These results suggest that LV stiffening in healthy ageing occurs during the transition between youth and middle-age and becomes manifest between the ages of 50 to 64. Thereafter, this LV stiffening is followed by LV volume contraction and remodelling after the age of 65.

The anthropology of motion: Historical methodology and humanities-related technology

Motion, movement in space from the standpoint of the development of man and society, the “instinct of movement” (which is inherent in modern sedentary humans as well), local and mainstream cultures in history, Nordicism and “hordism” as the mainstream dimensions of Russian mentality, and other aspects of a new trend in the humanities were discussed at a RAS Presidium meeting. The paper and discussion materials are published below.

Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans

Endurance and strength training are established as distinct exercise modalities, increasing either mitochondrial density or myofibrillar units. Recent research, however, suggests that mitochondrial biogenesis is stimulated by both training modalities. To test the training "specificity" hypothesis, mitochondrial respiration was studied in permeabilized muscle fibers from 25 sedentary adults after endurance (ET) or strength training (ST) in normoxia or hypoxia [fraction of inspired oxygen (Fi(O(2))) = 21% or 13.5%]. Biopsies were taken from the musculus vastus lateralis, and cycle-ergometric incremental maximum oxygen uptake (VO(2max)) exercise tests were performed under normoxia, before and after the 10-wk training program. The main finding was a significant increase (P < 0.05) of fatty acid oxidation capacity per muscle mass, after endurance and strength training under normoxia [2.6- and 2.4-fold for endurance training normoxia group (ET(N)) and strength training normoxia group (ST(N)); n = 8 and 3] and hypoxia [2.0-fold for the endurance training hypoxia group (ET(H)) and strength training hypoxia group (ST(H)); n = 7 and 7], and higher coupling control of oxidative phosphorylation. The enhanced lipid oxidative phosphorylation (OXPHOS) capacity was mainly (87%) due to qualitative mitochondrial changes increasing the relative capacity for fatty acid oxidation (P < 0.01). Mitochondrial tissue-density contributed to a smaller extent (13%), reflected by the gain in muscle mass-specific respiratory capacity with a physiological substrate cocktail (glutamate, malate, succinate, and octanoylcarnitine). No significant increase was observed in mitochondrial DNA (mtDNA) content. Physiological OXPHOS capacity increased significantly in ET(N) (P < 0.01), with the same trend in ET(H) and ST(H) (P < 0.1). The limitation of flux by the phosphorylation system was diminished after training. Importantly, key mitochondrial adaptations were similar after endurance and strength training, regardless of normoxic or hypoxic exercise. The transition from a sedentary to an active lifestyle induced muscular changes of mitochondrial quality representative of mitochondrial health.

Metabolic adaptation for low energy throughput in orangutans

Energy is the fundamental currency of life--needed for growth, repair, and reproduction--but little is known about the metabolic physiology and evolved energy use strategies of the great apes, our closest evolutionary relatives. Here we report daily energy use in free-living orangutans (Pongo spp.) and test whether observed differences in energy expenditure among orangutans, humans, and other mammals reflect known differences in life history. Using the doubly labeled water method, we measured daily energy expenditure (kCal/d) in orangutans living in a large indoor/outdoor habitat at the Great Ape Trust. Despite activity levels similar to orangutans in the wild, Great Ape Trust orangutans used less energy, relative to body mass, than nearly any eutherian mammal ever measured, including sedentary humans. Such an extremely low rate of energy use has not been observed previously in primates, but is consistent with the slow growth and low rate of reproduction in orangutans, and may be an evolutionary response to severe food shortages in their native Southeast Asian rainforests. These results hold important implications for the management of orangutan populations in captivity and in the wild, and underscore the flexibility and interdependence of physiological, behavioral, and life history strategies in the evolution of apes and humans.

Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

Sedentary behavior is associated with an attenuated thermogenic response to beta-adrenergic receptor (beta-AR) stimulation, an important regulator of energy expenditure (EE) in humans. Chronic stimulation of beta-ARs, via heightened activity of the sympathoadrenal system, leads to diminished beta-AR function. We have investigated the hypothesis that the thermogenic response of sedentary adults to beta-AR stimulation will be increased during short-term sympathoadrenal inhibition. Using a randomly ordered, repeated measures study design, resting EE (REE; indirect calorimetry, ventilated hood technique) and the % increase in EE above REE (%DeltaEE) during acute i.v. isoproterenol administration (nonselective beta-AR agonist; 6, 12, and 24 ng/kg fat-free mass per min) were determined in 16 sedentary adults (nine females and seven males, 25+/-1 years, body mass index: 26.1+/-0.9 kg/m(2), maximal oxygen uptake: 40+/-2 ml/kg per min (mean+/-s.e.m.)) in the basal state and on the 6th day of transdermal clonidine administration (centrally acting alpha2-AR agonist; 0.2 mg/day). Relative to baseline, clonidine inhibited sympathoadrenal activity, as evidenced by decreased plasma norepinephrine concentration (1.04+/-0.13 vs 0.34+/-0.03 nmol/l; P<0.001), skeletal muscle sympathetic nerve activity (22.5+/-3.8 vs 8.5+/-1.9 bursts/min; P=0.003), and resting heart rate (63+/-2 vs 49+/-1 beats/min; P<0.001). Sympathoadrenal inhibition decreased REE (6510+/-243 vs 5857+/-218 kJ/day; P<0.001), increased respiratory exchange ratio (0.84+/-0.01 vs 0.86+/-0.01; P=0.03), and augmented the thermogenic response to beta-AR stimulation (%DeltaEE: 11+/-2, 16+/-2, and 24+/-2 vs 14+/-1, 20+/-2, and 31+/-2; P=0.04). These data demonstrate that in sedentary humans, short-term inhibition of sympathoadrenal activity increases the thermogenic response to beta-AR stimulation, an important determinant of EE and hence energy balance.

Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet

The contemporary American diet figures centrally in the pathogenesis of numerous chronic diseases-'diseases of civilization'. We investigated in humans whether a diet similar to that consumed by our preagricultural hunter-gatherer ancestors (that is, a paleolithic type diet) confers health benefits. We performed an outpatient, metabolically controlled study, in nine nonobese sedentary healthy volunteers, ensuring no weight loss by daily weight. We compared the findings when the participants consumed their usual diet with those when they consumed a paleolithic type diet. The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleolithic type diet comprising lean meat, fruits, vegetables and nuts, and excluding nonpaleolithic type foods, such as cereal grains, dairy or legumes, for 10 days. Outcomes included arterial blood pressure (BP); 24-h urine sodium and potassium excretion; plasma glucose and insulin areas under the curve (AUC) during a 2 h oral glucose tolerance test (OGTT); insulin sensitivity; plasma lipid concentrations; and brachial artery reactivity in response to ischemia. Compared with the baseline (usual) diet, we observed (a) significant reductions in BP associated with improved arterial distensibility (-3.1+/-2.9, P=0.01 and +0.19+/-0.23, P=0.05);(b) significant reduction in plasma insulin vs time AUC, during the OGTT (P=0.006); and (c) large significant reductions in total cholesterol, low-density lipoproteins (LDL) and triglycerides (-0.8+/-0.6 (P=0.007), -0.7+/-0.5 (P=0.003) and -0.3+/-0.3 (P=0.01) mmol/l respectively). In all these measured variables, either eight or all nine participants had identical directional responses when switched to paleolithic type diet, that is, near consistently improved status of circulatory, carbohydrate and lipid metabolism/physiology. Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

Sympathetic Control in Physically Active and Sedentary Humans

Sympathetic Control in Physically Active and Sedentary Humans

Oxygen availability and PCr recovery rate in untrained human calf muscle: evidence of metabolic limitation in normoxia

In contrast to their exercise-trained counterparts, the maximal oxidative rate of skeletal muscle in sedentary humans appears not to benefit from supplemental O(2) availability but is impacted by severe hypoxia, suggesting a metabolic limitation either at or below ambient O(2) levels. However, the critical level of O(2) availability at which maximal metabolic rate is reduced in sedentary humans is unknown. Using (31)P magnetic resonance spectroscopy and arterial oximetry, phosphocreatine (PCr) recovery kinetics and arterial oxygenation were assessed in six sedentary subjects performing 5-min bouts of plantar flexion exercise followed by 6 min of recovery. Each trial was repeated while breathing one of four different fractions of inspired O(2) (FI(O(2))) (0.10, 0.12, 0.15, and 0.21). The PCr recovery rate constant (a marker of oxidative capacity) was unaffected by reductions in FI(O(2)), remaining at a value of 1.5 +/- 0.2 min(-1) until arterial O(2) saturation (Sa(O(2))) fell to less than approximately 92%, the average value reached breathing an FI(O(2)) of 0.15. Below this Sa(O(2)), the PCr rate constant fell significantly by 13 and 31% to 1.3 +/- 0.2 and 1.0 +/- 0.2 min(-1) (P < 0.05) as Sa(O(2)) was reduced to 82 +/- 3 and 77 +/- 2%, respectively. In conclusion, this study has revealed that O(2) availability does not impact maximal oxidative rate in sedentary humans until the O(2) level falls well below that of ambient air, indicating a metabolic limitation in normoxia.

Acute sympathetic vasoconstriction at rest and during dynamic exercise in cyclists and sedentary humans

The impact of exercise training on sympathetic activation is not well understood, especially across untrained and trained limbs in athletes. Therefore, in eight sedentary subjects (maximal oxygen consumption = 40 +/- 2 ml x kg(-1) x min(-1)) and eight competitive cyclists (maximal oxygen consumption = 64 +/- 2 ml x kg(-1) x min(-1)), we evaluated heart rate, blood pressure, blood flow, vascular conductance, and vascular resistance in the leg and arm during acute sympathetic stimulation [cold pressor test (CPT)]. The CPT was also performed during dynamic leg (knee extensor) or arm (handgrip) exercise at 50% of maximal work rate (WRmax) with measurements in the exercising limb. At rest, the CPT decreased vascular conductance similarly in the leg and arm of sedentary subjects (-33 +/- 8% leg, -38 +/- 6% arm) and cyclists (-34 +/- 4% leg, -31 +/- 9% arm), and during exercise CPT-induced vasoconstriction was blunted (i.e., sympatholysis) in both the leg and arm of both groups. However, the magnitude of sympatholysis was significantly different between the arm and leg of the sedentary group (-47 +/- 11% arm, -25 +/- 8% leg), and it was less in the arm of cyclists (-28 +/- 11%) than sedentary controls. Taken together, these data provide evidence that sympathetically mediated vasoconstriction is expressed equally and globally at rest in both sedentary and trained individuals, with a differential pattern of vasoconstriction during acute exercise according to limb and exercise training status.

Conjugated Linoleic Acid Decreases Insulin Sensitivity and Increases Skeletal Muscle Ceramides in Overweight, Sedentary Humans

BACKGROUND. The effect of conjugated linoleic acid (CLA) on insulin sensitivity (IS) in humans is controversial with some studies demonstrating an improvement and others a worsening of IS. In Zucker diabetic fatty rats, CLA improves IS and this is correlated with a reduction in intramuscular triglycerides (IMTG). Elelvated IMTG is associated with the development of insulin resistance; however it is likely the more reactive lipid species such as diglycerides (DG) and ceramides that cause insulin resistance by interfering with insulin signaling in skeletal muscle. To date, no research has attempted to measure skeletal muscle ceramide and DG content following CLA treatment. The PURPOSE of this research was to determine the effects of CLA on IS and skeletal muscle lipid content in overweight, non-diabetic humans. It is hypothesized that CLA will improve IS with an associated reduction in skeletal muscle IMTG, DG and ceramide content in skeletal muscle. METHODS: Nine overweight, non-diabetic, sedentary humans (BMI 29.6 ± 0.6 kg/m2, age 31.2 ± 3.7 yrs) were supplemented with 4 g of mixed isomer CLA/dfor 12 weeks. Subjects underwent oral glucose tolerance tests and resting skeletal muscle biopsies prior to and following supplementation. Total and individual species of skeletal muscle IMTG, DG and ceramides were measured prior to and following CLA treatment. Blood samples were assessed for glucose and insulin in response to the oral glucose tolerance test. RESULTS: Glucose and insulin area under the curves were significantly increased following CLA supplementation with a resultant 20 % decrease in insulin sensitivity (p <0.05). Total (prevs post 403.1 ±34.4 vs. 660.3 ± 144.0) and polyunsaturated (81.4 ± 9.0 vs. 148.3 ± 32.1) ceramide content was significantly increased following CLA supplementation (p < 0.05). There was a trend towards an increase in total saturated and monounsaturated fatty acid species (p <0.06). Total DG and IMTG were not changed following treatment. CONCLUSION. This research demonstrates that CLA supplementation decreases insulin sensitivity in overweight, sedentary individuals. This reduction in insulin sensitivity may have been the result of elevated skeletal muscle ceramide content interfering with enzymes involved with the insulin signaling pathway.

Comment on Point:Counterpoint “In health and in a normoxic environment, V̇o2 maxis/is not limited primarily by cardiac output and locomotor muscle blood flow”

Comment on Point:Counterpoint “In health and in a normoxic environment, V̇<scp>o</scp>_{2 max}is/is not limited primarily by cardiac output and locomotor muscle blood flow”

Exercise-induced oxidative stress leads hemolysis in sedentary but not trained humans

Intravascular hemolysis is one of the most emphasized mechanisms for destruction of erythrocytes during and after physical activity. Exercise-induced oxidative stress has been proposed among the different factors for explaining exercise-induced hemolysis. The validity of oxidative stress following exhaustive cycling exercise on erythrocyte damage was investigated in sedentary and trained subjects before and after antioxidant vitamin treatment (A, C, and E) for 2 mo. Exercise induced a significant increase in thiobarbituric acid-reactive substance and protein carbonyl content levels in sedentary subjects and resulted in an increase of osmotic fragility and decrease in deformability of erythrocytes, accompanied by signs for intravascular hemolysis (increase in plasma hemoglobin concentration and decrease in haptoglobulin levels). Administration of antioxidant vitamins for 2 mo prevented exercise-induced oxidative stress (thiobarbituric acid-reactive substance, protein carbonyl content) and deleterious effects of exhaustive exercise on erythrocytes in sedentary subjects. Trained subjects' erythrocyte responses to exercise were different from those of sedentary subjects before antioxidant vitamin treatment. Osmotic fragility and deformability of erythrocytes, plasma hemoglobin concentration, and haptoglobulin levels were not changed after exercise, although the increased oxidative stress was observed in trained subjects. After antioxidant vitamin treatment, functional and structural parameters of erythrocytes were not altered in the trained group, but exercise-induced oxidative stress was prevented. Increased percentage of young erythrocyte populations was determined in trained subjects by density separation of erythrocytes. These findings suggest that the exercise-induced oxidative stress may contribute to exercise-induced hemolysis in sedentary humans.

Angiogenic growth factor response to acute systemic exercise in human skeletal muscle.

We investigated whether acute systemic exercise increases vascular endothelial growth factor (VEGF), VEGF receptor (KDR and Flt-1) mRNA, and VEGF protein in sedentary humans. Twelve sedentary subjects were recruited and performed 1 h of acute, cycle ergometer exercise at 50% of maximal oxygen consumption. Muscle biopsies were obtained from the vastus lateralis before exercise and at 0, 2, and 4 h postexercise. Acute exercise significantly increased VEGF mRNA at 2 and 4 h and increased KDR and Flt-1 mRNA at 4 h postexercise. The sustained increase in VEGF mRNA through 4 h and the increases in KDR and Flt-1 at 4 h are different from their respective time course responses in rats. In contrast to the increase in VEGF mRNA postexercise, VEGF protein levels were decreased at 0 h postexercise. These results provide evidence in humans that 1) VEGF, KDR, and Flt-1 mRNA are increased by acute systemic exercise; 2) the time course of the VEGF, KDR, and Flt-1 mRNA responses are different from those previously reported in rats (Gavin TP and Wagner PD. Acta Physiol Scand 175: 201-209, 2002); and 3) VEGF protein is decreased immediately after exercise.

The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-CoA carboxylase-2 expression.

Endurance training has been shown to increase fat oxidation both at rest and during exercise. However, most exercise training studies have been performed at high exercise intensity in well-trained athletes, and not much is known about the effect of a low-intensity training program on fat oxidation capacity in lean sedentary humans. Here, we examine the effect of 3-month low-intensity training program on total and intramuscular triglyceride (IMTG)- and/or VLDL-derived fat oxidation capacity and skeletal muscle mRNA expression. Six healthy untrained subjects (aged 43 +/- 2 years, BMI 22.7 +/- 1.1 kg/ m(2), V(O)(2max) 3.2 +/- 0.2 l/min) participated in a supervised 12-week training program at 40% V(O)(2max) three times weekly. Total and plasma-derived fatty acid oxidation at rest and during 1 h exercise was measured using [(13)C]palmitate, and in a separate test, [(13)C]acetate recovery was determined. Muscle biopsies were taken after an overnight fast. Total fat oxidation during exercise increased from 1,241 +/- 93 to 1,591 +/- 130 micromol/min (P = 0.06), and IMTG- and/or VLDL-derived fatty acid oxidation increased from 236 +/- 84 to 639 +/- 172 micromol/min (P = 0.09). Acetyl-CoA carboxylase-2 mRNA expression was significantly decreased after training (P = 0.005), whereas lipoprotein lipase mRNA expression tended to increase (P = 0.07). In conclusion, a minimal amount of physical activity tends to increase fat oxidation and leads to marked changes in the expression of genes encoding for key enzymes in fat metabolism.

Insulin Pathway Takes a Jog: Workouts might benefit young and old by employing different molecular messengers (Insulin signaling)

Athletes of all ages can handle a sugar-laced Hershey bar better than their couch potato counterparts can. That's because workouts boost muscle cells' ability to respond to insulin, the hormone that instructs such cells to bring glucose aboard. Hitting the gym provides protection from the root cause of type II diabetes: insulin resistance, a condition in which muscle cells lose the ability to take up glucose efficiently even when insulin is present. But a new study suggests that hours spent riding a stationary bike might trigger different molecular tripwires in young and old people. The work highlights the importance of studying insulin resistance in older subjects. When insulin binds to a receptor attached to the exterior of a muscle cell, it sets off a sequence of events within. First it recruits several insulin receptor substrates (IRSs). IRS-1 then docks with and activates many other molecules, including phosphatidylinositol (PI) 3-kinase, which incites poorly defined cellular pathways that relay insulin's signal. As a result of this signaling cascade, the insulin-sensitive glucose transporter GLUT-4 moves to the muscle cell membrane, where it helps sugar flow into the cell. Scientists know little about how exercise affects the many molecular couriers that handle insulin's message before it reaches GLUT-4. Understanding the influence of exercise on these envoys might help pinpoint targets for drugs that can reverse or prevent insulin resistance, as workouts do. Finding such drug targets matters most to older people: After age 30, sedentary humans' resistance to insulin increases, rendering them vulnerable to high cholesterol levels, arterial damage, cardiac problems, hyperglycemia, obesity, and type II diabetes. To identify molecular messengers whose activity might change in response to exercise, Tanner and colleagues first examined the muscle tissue of otherwise sedentary young (19- to 28-year-old) men before and after a weeklong endurance exercise regimen. In that study, published a year ago, the subjects exhibited not only an enhanced response to insulin but also increased PI 3-kinase activity. Expecting the same result, the researchers placed nine inactive 50- to 70-year-old men on the same regimen and followed the same experimental protocol. Like in the young men, sugar in the older subjects' blood moved into cells more efficiently after the week's exercise than it had before the workouts. But, unlike the muscle cells of young men, those of older men showed little change in PI 3-kinase activity after the exercise program. Older men still experience the increased insulin sensitivity that comes with short-term exercise, but the new results suggest that they don't achieve it by boosting PI 3-kinase activity as young men do. Exercise might benefit the older men either by altering a molecular messenger in the murky realm downstream of PI 3-kinase or by exploiting a signaling pathway that doesn't involve PI 3-kinase. Further study of more people at more time points and over a longer course of exercise is required to confirm the findings. But the results introduce a new possibility for how exercise impacts insulin signaling with age. Understanding the disparity between young and old people's responses to exercise might help scientists develop additional ways to maintain insulin sensitivity in older adults. --Katharine Miller; suggested by James M. Harper C. J. Tanner, T. R. Koves, R. L. Cortright, W. J. Pories, Y.-B. Kim, B. B. Kahn, G. L. Dohm, J. A. Houmard, Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in middle-aged men. Am. J. Physiol. Endocrinol. Metab. 282 , E147-E153 (2002). [Abstract] [Full Text]

Respiratory muscle training increases cycling endurance without affecting cardiovascular responses to exercise.

We tested whether the increased cycling endurance observed after respiratory muscle training (RMT) in healthy sedentary humans was associated with a training-induced increase in cardiac stroke volume (SV) during exercise, similar to the known effect of endurance training. Thirteen subjects underwent RMT by normocapnic hyperpnea, nine underwent aerobic endurance training (cycling and/or running) and fifteen served as non-training controls. Training comprised 40 sessions performed within 15 weeks, where each session lasted 30 min. RMT increased cycling endurance at 70% maximal aerobic power (Wmax) by 24% [mean (SD) 35.6 (11.9) min vs 44.2 (17.6) min, P < 0.05], but SV at 60% Wmax was unchanged [94 (21) ml vs 93 (20) ml]. Aerobic endurance training increased both SV [89 (24) ml vs 104 (32) ml, P < 0.01] and cycling endurance [37.4 (12.8) min vs 52.6 (16.9) min, P < 0.01]. In the control group, no changes were observed in any of these variables. It is concluded that the increased cycling endurance that is observed after RMT is not due to cardiovascular adaptations, and that the results provide evidence for the role of the respiratory system as an exercise-limiting factor.