Exercise training increases intramyocellular lipid and oxidative capacity in older adults

Intramyocellular lipid (IMCL) has been associated with insulin resistance. However, an association between IMCL and insulin resistance might be modulated by oxidative capacity in skeletal muscle. We examined the hypothesis that 12 wk of exercise training would increase both IMCL and the oxidative capacity of skeletal muscle in older (67.3 +/- 0.7 yr), previously sedentary subjects (n = 13; 5 men and 8 women). Maximal aerobic capacity (Vo(2 max)) increased from 1.65 +/- 0.20 to 1.85 +/- 0.14 l/min (P < 0.05), and systemic fat oxidation induced by 1 h of cycle exercise at 45% of Vo(2 max) increased (P < 0.05) from 15.03 +/- 40 to 19.29 +/- 0.80 (micromol.min(-1).kg fat-free mass(-1)). IMCL, determined by quantitative histological staining in vastus lateralis biopsies, increased (P < 0.05) from 22.9 +/- 1.9 to 25.9 +/- 2.6 arbitrary units (AU). The oxidative capacity of muscle, determined by succinate dehydrogenase staining intensity, significantly increased (P < 0.05) from 75.2 +/- 5.2 to 83.9 +/- 3.6 AU. The percentage of type I fibers significantly increased (P < 0.05) from 35.4 +/- 2.1 to 40.1 +/- 2.3%. In conclusion, exercise training increases IMCL in older persons in parallel with an enhanced capacity for fat oxidation.     

Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study.

The aim of the present study was to establish fat oxidation rates over a range of exercise intensities in a large group of healthy men and women. It was hypothesised that exercise intensity is of primary importance to the regulation of fat oxidation and that gender, body composition, physical activity level, and training status are secondary and can explain part of the observed interindividual variation. For this purpose, 300 healthy men and women (157 men and 143 women) performed an incremental exercise test to exhaustion on a treadmill [adapted from a previous protocol (Achten J, Venables MC, and Jeukendrup AE. Metabolism 52: 747-752, 2003)]. Substrate oxidation was determined using indirect calorimetry. For each individual, maximal fat oxidation (MFO) and the intensity at which MFO occurred (Fat(max)) were determined. On average, MFO was 7.8 +/- 0.13 mg.kg fat-free mass (FFM)(-1).min(-1) and occurred at 48.3 +/- 0.9% maximal oxygen uptake (Vo(2 max)), equivalent to 61.5 +/- 0.6% maximal heart rate. MFO (7.4 +/- 0.2 vs. 8.3 +/- 0.2 mg.kg.FFM(-1).min(-1); P < 0.01) and Fat(max) (45 +/- 1 vs. 52 +/- 1% Vo(2 max); P < 0.01) were significantly lower in men compared with women. When corrected for FFM, MFO was predicted by physical activity (self-reported physical activity level), Vo(2 max), and gender (R(2) = 0.12) but not with fat mass. Men compared with women had lower rates of fat oxidation and an earlier shift to using carbohydrate as the dominant fuel. Physical activity, Vo(2 max), and gender explained only 12% of the interindividual variation in MFO during exercise, whereas body fatness was not a predictor. The interindividual variation in fat oxidation remains largely unexplained.     

Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity

Impaired mitochondrial function and structure and intramyocellular lipid (IMCL) accumulation have been associated with obesity and Type 2 diabetes. We examined whether endurance exercise training and sex influenced IMCL and mitochondrial morphology using electron microscopy, whole-body substrate use, and mitochondrial enzyme activity. Untrained men (n = 5) and women (n = 7) were tested before and after 7 wk of endurance exercise training. Testing included 90 min of cycle ergometry at 60% Vo(2 peak) with preexercise muscle biopsies analyzed for IMCL and mitochondrial size/area using electron microscopy and short-chain beta-hydroxyacyl-CoA dehydrogenase (SCHAD) and citrate synthase (CS) enzyme activity. Training increased the mean lipid area density (P = 0.090), the number of IMCL droplets (P = 0.055), the number of IMCL droplets in contact with mitochondria (P = 0.010), the total mitochondrial area (P < 0.001), and the size of individual mitochondrial fragments (P = 0.006). Women had higher mean lipid area density (P = 0.030) and number of IMCL droplets (P = 0.002) before and after training, but higher individual IMCL area only before training (P = 0.013), compared with men. Women oxidized more fat (P = 0.027) and less carbohydrate (P = 0.032) throughout the study. Training increased Vo(2 peak) (P < 0.001), %fat oxidation (P = 0.018), SCHAD activity (P = 0.003), and CS activity (P = 0.042). In summary, endurance exercise training increased IMCL area density due to an increase in the number of lipid droplets, whereas the increase in total mitochondrial area was due to an increase in the size of individual mitochondrial fragments. In addition, women have higher IMCL content compared with men due mainly to a greater number of individual droplets. Finally, endurance exercise training increased the proportion of IMCL in physical contact with mitochondria.     

Effect of exercise training at different intensities on fat metabolism of obese men.

The present study investigated the effect of exercise training at different intensities on fat oxidation in obese men. Twenty-four healthy male obese subjects were randomly divided in either a low- [40% maximal oxygen consumption (VO(2 max))] or high-intensity exercise training program (70% VO(2 max)) for 12 wk, or a non-exercising control group. Before and after the intervention, measurements of fat metabolism at rest and during exercise were performed by using indirect calorimetry, [U-(13)C]palmitate, and [1,2-(13)C]acetate. Furthermore, body composition and maximal aerobic capacity were measured. Total fat oxidation did not change at rest in any group. During exercise, after low-intensity exercise training, fat oxidation was increased by 40% (P < 0.05) because of an increased non-plasma fatty acid oxidation (P < 0.05). High-intensity exercise training did not affect total fat oxidation during exercise. Changes in fat oxidation were not significantly different among groups. It was concluded that low-intensity exercise training in obese subjects seemed to increase fat oxidation during exercise but not at rest. No effect of high-intensity exercise training on fat oxidation could be shown.     

Three weeks of caloric restriction alters protein metabolism in normal-weight, young men

The effects of prolonged caloric restriction (CR) on protein kinetics in lean subjects has not been investigated previously. The purpose of this study was to test the hypotheses that 21 days of CR in lean subjects would 1) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation and 2) negatively impact exercise performance. Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1). Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool model in the postabsorptive state during rest and 50 min of exercise (EX) at 50% of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise performance were measured throughout the intervention. At rest, leucine flux (approximately 131 micromol.kg(-1).h(-1)) and oxidation (R(ox); approximately 19 micromol.kg(-1).h(-1)) did not differ pre- and post-CR. During EX, leucine flux (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR than they were pre-CR. Nitrogen balance was negative throughout the intervention ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric restriction reduced leucine flux and R(ox) during exercise in normal-weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.     

A moderate-intensity exercise program fulfilling the American College of Sports Medicine net energy expenditure recommendation improves health outcomes in premenopausal women

The purpose of this study was to assess and quantify the health outcomes associated with a moderate-intensity (50% VO2R) exercise program designed to achieve the American College of Sports Medicine net caloric expenditure guideline of 1,000 kcal x wk(-1). Fifteen apparently healthy but sedentary premenopausal women with the baseline characteristics (mean +/- SD age, height, weight, body composition, and VO2max: 37.4 +/- 6.3 yr, 166.2 +/- 6.2 cm, 72.1 +/- 11.2 kg, 32.5 +/- 5.8%, and 34.8 +/- 5.8 mL x kg(-1) x min(-1), respectively) participated in and completed the study. Exercise training was performed 3-4 days per week for 10 weeks in a progressive manner at moderate intensity (50% VO2R). There were significant (P < 0.05) improvements in VO2max (+2.5 mL x kg(-1) x min(-1)), systolic (-13.7 mm Hg) and diastolic (-6.4 mm Hg) blood pressure, high-density lipoprotein cholesterol (+3.2 mg x dL(-1)), fasting blood glucose (-4.9 mg x dL(-1)), and percent body fat (-1.6%). Although the American College of Sports Medicine specifies that the energy expenditure goal should be a net caloric expenditure of 1,000 kcal x wk(-1) and classifies relative moderate intensity as 40-59% of heart rate reserve or VO2R, we are unaware of any previous investigations that have examined the specific health outcomes associated with an exercise program fulfilling these requirements. Results indicate that significant health benefits will be conferred to previously sedentary, premenopausal women who engage in a moderate-intensity, 10-week exercise program designed to fulfill the net energy expenditure guideline of 1,000 kcal x wk(-1).     

Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training

To evaluate the contribution of working muscle to whole body lipid oxidation, we examined the effects of exercise intensity and endurance training (9 wk, 5 days/wk, 1 h, 75% Vo(2 peak)) on whole body and leg free fatty acid (FFA) kinetics in eight male subjects (26 +/- 1 yr, means +/- SE). Two pretraining trials [45 and 65% Vo(2 max) (45UT, 65UT)] and two posttraining trials [65% of pretraining Vo(2 peak) (ABT), and 65% of posttraining Vo(2 peak) (RLT)] were performed using [1-(13)C]palmitate infusion and femoral arteriovenous sampling. Training increased Vo(2 peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 ml.kg(-1).min(-1), P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX) compared with rest regardless of workload or training status ( approximately 20 vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest ( approximately -36 micromol/min) to net uptake during EX for 45UT (179 +/- 75), ABT (236 +/- 63), and RLT (136 +/- 110) (P < 0.05), but not 65UT (51 +/- 127). Leg FFA tracer measured uptake was higher during EX than rest for all trials and greater during posttraining in RLT (716 +/- 173 micromol/min) compared with pretraining (45UT 450 +/- 80, 65UT 461 +/- 72, P < 0.05). Leg muscle lipid oxidation increased with training in ABT (730 +/- 163 micromol/min) vs. 65UT (187 +/- 94, P < 0.05). Leg muscle lipid oxidation represented approximately 62 and 30% of whole body lipid oxidation at lower and higher relative intensities, respectively. In summary, training can increase working muscle tracer measured FFA uptake and lipid oxidation for a given power output, but both before and after training the association between whole body and leg lipid metabolism is reduced as exercise intensity increases.     

Changes in cardiorespiratory fitness and coronary heart disease risk factors following 24 wk of moderate- or high-intensity exercise of equal energy cost.

This study was designed to investigate the effect of exercise intensity on cardiorespiratory fitness and coronary heart disease risk factors. Maximum oxygen consumption (Vo(2 max)), lipid, lipoprotein, and fibrinogen concentrations were measured in 64 previously sedentary men before random allocation to a nonexercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of Vo(2 max)), or a high-intensity exercise group (three 400-kcal sessions per week at 80% of Vo(2 max)). Subjects were instructed to maintain their normal dietary habits, and training heart rates were represcribed after monthly fitness tests. Forty-two men finished the study. After 24 wk, Vo(2 max) increased by 0.38 +/- 0.14 l/min in the moderate-intensity group and by 0.55 +/- 0.27 l/min in the high-intensity group. Repeated-measures analysis of variance identified a significant interaction between monthly Vo(2 max) score and exercise group (F = 3.37, P < 0.05), indicating that Vo(2 max) responded differently to moderate- and high-intensity exercise. Trend analysis showed that total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and fibrinogen concentrations changed favorably across control, moderate-intensity, and high-intensity groups. However, significant changes in total cholesterol (-0.55 +/- 0.81 mmol/l), low-density lipoprotein cholesterol (-0.52 +/- 0.80 mmol/l), and non-high-density lipoprotein cholesterol (-0.54 +/- 0.86 mmol/l) were only observed in the high-intensity group (all P < 0.05 vs. controls). These data suggest that high-intensity training is more effective in improving cardiorespiratory fitness than moderate-intensity training of equal energy cost. These data also suggest that changes in coronary heart disease risk factors are influenced by exercise intensity.     

Beneficial metabolic adaptations due to endurance exercise training in the fasted state

Training with limited carbohydrate availability can stimulate adaptations in muscle cells to facilitate energy production via fat oxidation. Here we investigated the effect of consistent training in the fasted state, vs. training in the fed state, on muscle metabolism and substrate selection during fasted exercise. Twenty young male volunteers participated in a 6-wk endurance training program (1-1.5 h cycling at ～70% Vo(?max), 4 days/wk) while receiving isocaloric carbohydrate-rich diets. Half of the subjects trained in the fasted state (F; n = 10), while the others ingested ample carbohydrates before (～160 g) and during (1 g·kg body wt?1·h?1) the training sessions (CHO; n = 10). The training similarly increased Vo(?max) (+9%) and performance in a 60-min simulated time trial (+8%) in both groups (P < 0.01). Metabolic measurements were made during a 2-h constant-load exercise bout in the fasted state at ～65% pretraining Vo(?max). In F, exercise-induced intramyocellular lipid (IMCL) breakdown was enhanced in type I fibers (P < 0.05) and tended to be increased in type IIa fibers (P = 0.07). Training did not affect IMCL breakdown in CHO. In addition, F (+21%) increased the exercise intensity corresponding to the maximal rate of fat oxidation more than did CHO (+6%) (P < 0.05). Furthermore, maximal citrate synthase (+47%) and β-hydroxyacyl coenzyme A dehydrogenase (+34%) activity was significantly upregulated in F (P < 0.05) but not in CHO. Also, only F prevented the development exercise-induced drop in blood glucose concentration (P < 0.05). In conclusion, F is more effective than CHO to increase muscular oxidative capacity and at the same time enhances exercise-induced net IMCL degradation. In addition, F but not CHO prevented drop of blood glucose concentration during fasting exercise.     

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

In this study, we compared the effects of endurance training in the fasted state (F) vs. the fed state [ample carbohydrate intake (CHO)] on exercise-induced intramyocellular lipid (IMCL) and glycogen utilization during a 6-wk period of a hypercaloric (～+30% kcal/day) fat-rich diet (HFD; 50% of kcal). Healthy male volunteers (18-25 yrs) received a HFD in conjunction with endurance training (four times, 60-90 min/wk) either in F (n = 10) or with CHO before and during exercise sessions (n = 10). The control group (n = 7) received a HFD without training and increased body weight by ～3 kg (P < 0.001). Before and after a HFD, the subjects performed a 2-h constant-load bicycle exercise test in F at ～70% maximal oxygen uptake rate. A HFD, both in the absence (F) or presence (CHO) of training, elevated basal IMCL content by ～50% in type I and by ～75% in type IIa fibers (P < 0.05). Independent of training in F or CHO, a HFD, as such, stimulated exercise-induced net IMCL breakdown by approximately twofold in type I and by approximately fourfold in type IIa fibers. Furthermore, exercise-induced net muscle glycogen breakdown was not significantly affected by a HFD. It is concluded that a HFD stimulates net IMCL degradation by increasing basal IMCL content during exercise in type I and especially IIa fibers. Furthermore, a hypercaloric HFD provides adequate amounts of carbohydrates to maintain high muscle glycogen content during training and does not impair exercise-induced muscle glycogen breakdown.     

Aging attenuates vascular and metabolic plasticity but does not limit improvement in muscle VO(2) max

The interactions between exercise, vascular and metabolic plasticity, and aging have provided insight into the prevention and restoration of declining whole body and small muscle mass exercise performance known to occur with age. Metabolic and vascular adaptations to normoxic knee-extensor exercise training (1 h 3 times a week for 8 wk) were compared between six sedentary young (20 +/- 1 yr) and six sedentary old (67 +/- 2 yr) subjects. Arterial and venous blood samples, in conjunction with a thermodilution technique facilitated the measurement of quadriceps muscle blood flow and hematologic variables during incremental knee-extensor exercise. Pretraining, young and old subjects attained a similar maximal work rate (WR(max)) (young = 27 +/- 3, old = 24 +/- 4 W) and similar maximal quadriceps O(2) consumption (muscle Vo(2 max)) (young = 0.52 +/- 0.03, old = 0.42 +/- 0.05 l/min), which increased equally in both groups posttraining (WR(max), young = 38 +/- 1, old = 36 +/- 4 W, Muscle Vo(2 max), young = 0.71 +/- 0.1, old = 0.63 +/- 0.1 l/min). Before training, muscle blood flow was approximately 500 ml lower in the old compared with the young throughout incremental knee-extensor exercise. After 8 wk of knee-extensor exercise training, the young reduced muscle blood flow approximately 700 ml/min, elevated arteriovenous O(2) difference approximately 1.3 ml/dl, and increased leg vascular resistance approximately 17 mmHg x ml(-1) x min(-1), whereas the old subjects revealed no training-induced changes in these variables. Together, these findings indicate that after 8 wk of small muscle mass exercise training, young and old subjects of equal initial metabolic capacity have a similar ability to increase quadriceps muscle WR(max) and muscle Vo(2 max), despite an attenuated vascular and/or metabolic adaptation to submaximal exercise in the old.     

Predictors of sweat loss in man during prolonged exercise

Nineteen healthy male subjects, differing in training status and Vo2max (52 +/- 1 ml.min-1.kg-1, mean +/- SEM; 43-64 ml.min-1.kg-1, range), exercised for 1 h at an absolute workload of 192 +/- 8 W (140-265 W); this was equivalent to 70 +/- 1% Vo2max (66-74%). Each exercise test was performed on an electrically braked cycle ergometer at a constant ambient temperature (22.5 +/- 0.0 degrees C) and relative humidity (85 +/- 0%). Nude body weight was recorded prior to and after each exercise test. Absolute sweat loss (body weight loss corrected for respiratory weight loss) during each test was 910 +/- 82 g (426-1665 g); this was equivalent to 1.3 +/- 0.1% (0.7-2.2%) of pre-exercise body weight (relative sweat loss). Weighted mean skin temperature and rectal temperature increased after 5 min of exercise from 30.5 +/- 0.3 degrees C and 37.2 +/- 0.1 degrees C respectively to 32.5 +/- 0.2 degrees C and 38.8 +/- 0.1 degrees C respectively, recorded immediately prior to the end of exercise. Bivariate linear regression and Pearson's correlation demonstrated absolute sweat loss was related to Vo2max (r = 0.72, p less than 0.001), absolute exercise workload (r = 0.66, p less than 0.01), body surface area (r = 0.62, p less than 0.01), weight (r = 0.60, p less than 0.01) and height (r = 0.53, p less than 0.05). Relative sweat loss was related to VO2max (r = 0.77, P less than 0.001) and absolute exercise workload (R = 0.59, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution.

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls (n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 +/- 11.5 vs. 85.1 +/- 13.2 institutional units (IU); P = 0.007] and soleus [643.7 +/- 61.0 vs. 443.6 +/- 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 +/- 2.3 vs. 35.0 +/- 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 +/- 1.1 vs. 15.6 +/- 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 +/- 11.3 vs. 74.4 +/- 12.3 cm2, P = 0.004), triglycerides (131.1 +/- 11.0 vs. 66.3 +/- 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 +/- 0.9 vs. 7.0 +/- 0.9 microIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = -0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (beta = -633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.     

Longitudinal changes in energy expenditure and body composition in obese women with normal and impaired glucose tolerance

Our primary objective was to evaluate changes in energy expenditure and body composition in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). A secondary objective was to examine the relationship between maternal leptin and nutrient metabolism. Fifteen obese women, eight with NGT and seven with GDM, were evaluated before conception (P), at 12-14 wk (E), and at 34-36 wk (L). Energy expenditure and glucose and fat metabolism were measured using indirect calorimetry. Basal hepatic glucose production was measured using [6,6-2H2]glucose and insulin sensitivity by euglycemic clamp. There was a significant increase (6.6 kg, P = 0.0001) in fat mass from P to L. There was a 30% (P = 0.0001) increase in basal O2 consumption (VO2, ml/min). There were no significant changes in carbohydrate oxidation during fasting or storage from P to L. There was, however, a significant (P = 0.0001) 150% increase in basal fat oxidation (mg/min) from P to L. Under hyperinsulinemic conditions, there were similar 25% increases in VO2 (P = 0.0001) from P to L in both groups. Because of the significant increases in insulin resistance from P to L, there was a significant (P = 0.0001) decrease in carbohydrate oxidation and storage. There was a net change from lipogenesis to lipolysis, i.e., fat oxidation (30-40 mg/min, P = 0.0001) from P to L. Serum leptin concentrations had a significant positive correlation with fat oxidation at E (r = 0.76, P = 0.005) and L (r = 0.72, P = 0.009). Pregnancy in obese women is associated with significant increases in fat mass and basal metabolic rate and an increased reliance on lipids both in the basal state and during the clamp. These modifications are similar in women with NGT and GDM. The increased reliance on fat metabolism is accompanied by a concomitant decrease in carbohydrate metabolism during hyperinsulinemia. The increase in fat oxidation may be related to increased maternal serum leptin.     

The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise

The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (Vo(2 peak) 60.7 +/- 1.6, n = 8) and untrained subjects (39.5 +/- 2.0 ml.min(-1).kg(-1), n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49-93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r = 0.62, P = 0.03), but was not different between trained (62 +/- 5%) and untrained subjects (72 +/- 2%). MFO was correlated to RER during submaximal exercise at 80 (r = -0.62, P = 0.02) and 120 W (r = -0.71, P = 0.007) and interpolated 35% Vo(2 peak) (r = -0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.     

Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle

Leptin acutely stimulates skeletal muscle fatty acid (FA) metabolism in lean rodents and humans. This stimulatory effect is eliminated following the feeding of high-fat diets in rodents as well as in obese humans. The mechanism(s) responsible for the development of skeletal muscle leptin resistance is unknown; however, a role for increased suppressor of cytokine signaling-3 (SOCS3) inhibition of the leptin receptor has been demonstrated in other rodent tissues. Furthermore, whether exercise intervention is an effective strategy to prevent or attenuate the development of skeletal muscle leptin resistance has not been investigated. Toward this end, 48 Sprague-Dawley rats (175-190 g; approximately 2-3 mo of age) were fed control or high-fat (60% kcal) diets for 4 wk and either remained sedentary or were treadmill trained. In control diet-fed animals that remained sedentary (CS) or were endurance trained (CT), leptin stimulated FA oxidation (CS +32 +/- 15%, CT +30 +/- 17%; P < 0.05), suppressed triacylglycerol (TAG) esterification (CS -17 +/- 7%, CT -24 +/- 8%; P < 0.05), and reduced the esterification-to-oxidation ratio (CS -19 +/- 13%, CT -29 +/- 10%; P < 0.001) in soleus muscle. High-fat feeding induced leptin resistance in the soleus of sedentary rats (FS), whereas endurance exercise training (FT) restored the ability of leptin to suppress TAG esterification (-19 +/- 9%, P = 0.038). Training did not completely restore the ability of leptin to stimulate FA oxidation. High-fat diets stimulated SOCS3 mRNA expression irrespective of training status (FS +451 +/- 120%, P = 0.024; FT +381 +/- 141%, P = 0.023). Thus the development of skeletal muscle leptin resistance appears to involve an increase in SOCS3 mRNA expression. Endurance training was generally effective in preventing the development of leptin resistance, although this did not appear to require a decrease in SOCS3 expression. Future studies should examine changes in the actual protein content of SOCS3 in muscle and establish whether aerobic exercise is also effective in treating leptin resistance in humans.     

Normal insulin sensitivity and IMCL content in overweight humans are associated with higher fasting lipid oxidation

Intramyocellular lipid (IMCL) storage is considered a local marker of whole body insulin resistance; because increments of body weight are supposed to impair insulin sensitivity, this study was designed to assess IMCL content, lipid oxidation, and insulin action in individuals with a moderate increment of body fat mass and no family history of diabetes. We studied 14 young, nonobese women with body fat <30% (n = 7) or >30% (n = 7) and 14 young, nonobese men with body fat <25% (n = 7) or >25% (n = 7) by means of the euglycemic-insulin clamp to assess whole body glucose metabolism, with indirect calorimetry to assess lipid oxidation, by localized (1)H NMR spectroscopy of the calf muscles to assess IMCL content, and with dual-energy X-ray absorptiometry to assess body composition. Subjects with higher body fat had normal insulin-stimulated glucose disposal (P = 0.80), IMCL content in both soleus (P = 0.22) and tibialis anterior (P = 0.75) muscles, and plasma free fatty acid levels (P = 0.075) compared with leaner subjects in association with increased lipid oxidation (P < 0.05), resting energy expenditure (P = 0.046), resting oxygen consumption (P = 0.049), and plasma leptin levels (P < 0.01) in the postabsorptive condition. In conclusion, in overweight subjects, preservation of insulin sensitivity was combined with increased lipid oxidation and maintenance of normal IMCL content, suggesting that abnormalities of these factors may mutually determine the development of insulin resistance associated with weight gain.     

Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat.

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P < 0.0001), decreased body weight (P < 0.0001) and fat mass (P < 0.001), while fat-free mass was not altered (P > 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.     

IMCL area density, but not IMCL utilization, is higher in women during moderate-intensity endurance exercise, compared with men

Women use more fat during endurance exercise as evidenced by a lower respiratory exchange ratio (RER). The contribution of intramyocellular lipid (IMCL) to lipid oxidation during endurance exercise is controversial, and studies investigating sex differences in IMCL utilization have found conflicting results. We determined the effect of sex on net IMCL use during an endurance exercise bout using an ultrastructural evaluation. Men (n = 17) and women (n = 19) completed 90-min cycling at 63% Vo(2peak). Biopsies were taken before and after exercise and fixed for electron microscopy to determine IMCL size, # IMCL/area, IMCL area density, and the % IMCL touching mitochondria. Women had a lower RER and carbohydrate oxidation rate and a higher lipid oxidation rate during exercise (P < 0.05), compared with men. Women had a higher # IMCL/area and IMCL area density (P < 0.05), compared with men. Women, but not men, had a higher % IMCL touching mitochondria postexercise (P = 0.03). Exercise decreased IMCL area density (P = 0.01), due to a decrease in the # IMCL/area (P = 0.02). There was no sex difference in IMCL size or net use. In conclusion, women have higher IMCL area density compared with men, due to an increased # IMCL and not an increased IMCL size, as well as an increased % IMCL touching mitochondria postexercise. Endurance exercise resulted in a net decrease in IMCL density due to decreased number of IMCL, not decreased IMCL size, in both sexes.     

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.