Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise.

The present study was intended to investigate the different components of fatty acid utilization during a 60-min period of moderate-intensity cycling exercise (50% of VO2max) in eight male type 2 diabetic subjects (aged 52.6 +/- 3.1 years, body fat 35.8 +/- 1.3%) and eight male obese control subjects (aged 45.1 +/- 1.4 years, body fat 34.2 +/- 1.3%) matched for age, body composition, and maximal aerobic capacity. To quantitate the different components of fatty acid metabolism, an isotope infusion of [U-13C]-palmitate was used in combination with indirect calorimetry. In separate experiments, the 13C label recovery in expired air was determined during infusion of [1,2-13C]-acetate (acetate recovery factor). There were no differences in energy expenditure or carbohydrate and total fat oxidation between the groups. The rate of appearance (Ra) of free fatty acid (FFA) (P < 0.05) and the exercise-induced increase in Ra of FFA were significantly lower (P < 0.05) in type 2 diabetic subjects compared with control subjects (baseline vs. exercise [40-60 min]; type 2 diabetes 11.9 +/- 0.9 vs. 19.6 +/- 2.2 micromol x kg(-1) fat-free mass [FFM] x min(-1) and control 15.8 +/- 1.8 vs. 28.6 +/- 2.1 micromol x kg(-1) FFM x min(-1)). The oxidation of plasma-derived fatty acids was significantly lower in type 2 diabetic subjects during both conditions (P < 0.05, baseline vs. exercise [40-60 min]; type 2 diabetes 4.2 +/- 0.5 vs. 14.1 +/- 1.9 micromol x kg(-1) FFM x min(-1) and control 6.2 +/- 0.6 vs. 20.4 +/- 1.9 micromol x kg(-1) FFM x min(-1)), whereas the oxidation of triglyceride-derived fatty acids was higher (P < 0.05). It is hypothesized that these impairments in fatty acid utilization may play a role in the etiology of skeletal muscle and hepatic insulin resistance.

Short-term effects of weight loss with or without low-intensity exercise training on fat metabolism in obese men.

BACKGROUND: Energy restriction is known to induce a decline in fat oxidation during the postdiet period. Reduced fat oxidation may contribute to weight regain. OBJECTIVE: The present study investigated the effect of the addition of low-intensity exercise training to energy restriction on postdiet fat oxidation and on the contribution of the sympathetic nervous system to fat oxidation. DESIGN: Forty obese men were divided randomly into 2 groups: diet (D) and diet plus exercise (DE). Both groups followed an energy restriction program for 10 wk. Subjects in the DE group also participated in a low-intensity exercise training program [40% maximal oxygen uptake (VO2max)] for 12 wk. Before the intervention and after 12 wk, with subjects at stable body weights, we measured body composition, VO2max, and substrate oxidation at rest, during exercise at 50% VO2max, and during recovery. Measurements were made with and without administration of the beta-adrenergic antagonist propranolol. RESULTS: Both interventions led to significant decreases in body weight, fat mass, and fat-free mass (P < 0.001); these decreases did not differ significantly between the D and DE groups. Neither intervention significantly affected VO2max. The effect of the intervention on the respiratory exchange ratio differed significantly between the D and DE groups [two-way analysis of variance (ANOVA), P < 0.05]. The effect on the beta-adrenergic-mediated respiratory exchange ratio tended to be different between the 2 groups (two-way ANOVA, P = 0.09). CONCLUSION: Addition of low-intensity exercise training to energy restriction counteracts the decline in fat oxidation during the postdiet period.

The effect of weight loss with or without exercise training on large artery compliance in healthy obese men.

BACKGROUND: Obesity is an independent risk factor for cardiovascular morbidity and mortality. Large artery compliance is thought to be associated with cardiovascular risk. The effect of weight loss on large artery compliance is not yet clarified. OBJECTIVE: To investigate the effect of weight loss, with or without exercise, on vessel wall properties in healthy obese men. DESIGN: This was a pair-matched randomized intervention study. All subjects were on an energy-restricted diet. One subject from each pair was also on an exercise programme. Measurements were performed before and at the end of the study period. The study lasted for 3 months. METHODS: The vessel wall properties of the brachial and common carotid artery were assessed using a vessel wall movement detector system in combination with applanation tonometry. RESULTS: The mean body mass index was 32.3+/-0.4 kg/m2 and decreased (P < 0.001) to 27.6+/-0.4 kg/mm2 during the study. The mean blood pressure decreased (P < 0.001) by 6%. At operating pressures, carotid artery distensibility was 27.5+/-1.7 x 10(-3)/kPa at the start of the study and 31.1+/-1.8 x 10(-3)/kPa (P < 0.04) at the end of the study. Brachial and carotid artery compliances were 0.11+/-0.01 and 1.35+/-0.08 mm2/kPa at the start of the study and tended to increase to 0.12+/-0.001 (P = 0.06) and 1.48+/-0.08 mm2/kPa (P = 0.057), respectively, at the end of the study. Isobaric compliance did not change. The diet-and-exercise group did not differ statistically from the only-diet group in the effects on weight loss, blood pressure and arterial compliance. CONCLUSION: This study shows that weight loss increased carotid artery distensibility at operating pressures, but not under isobaric conditions. This increase is probably due to the decrease in blood pressure. The addition of exercise did not result in an additional effect within 3 months.

Effects of dietary restraint vs exercise during weight maintenance in obese men.

OBJECTIVE: To investigate the effect of dietary restraint with or without exercise during weight maintenance after energy restriction. SUBJECTS AND METHODS: In total, 40 obese male subjects (mean BMI 32.3 kg/m(2); mean age 39 y) were recruited and randomly divided into a diet (D; n=20) and a diet plus exercise (DE; n=20) group. Both groups participated in an energy restriction programme (ER), which was followed by a weight maintenance phase (WM). Subjects in the DE also participated in an exercise programme. Body mass (BM) and the scores on the three factor eating questionnaire (TFEQ) were measured before and after the ER and after WM. RESULTS: No significant differences between both groups were found. All data taken together showed that BM loss during ER was explained by initial BM (r(2)=0.3, P<0.0005) and inversely by initial cognitive restraint (F1) (r(2)=0.4, P<0.0005) in a stepwise regression. BM regain during WM was explained by BM loss (r(2)=0.5, P<0.001) and by increase in F1 during ER (r(2)=0.6, P<0.001), while the exercise intervention did not contribute further to the explained variation. Subjects with a relatively high diet frequency prior to the study had relatively significant higher initial F1 scores (P<0.05). During ER, increase in F1 was associated with decrease in general hunger (F3). CONCLUSION: Successful BM loss was associated with higher initial BM and lower initial F1. Successful WM was explained by BM loss and increase in F1 during ER, irrespective of possible exercise training effects. Successful WM was reduced when F1 scores reach their limit, due to diet-frequency.

The effect of exercise training on beta-adrenergic stimulation of fat metabolism in obese men.

OBJECTIVE: To investigate the in vivo effect of exercise training at high and low intensity on beta-adrenergic stimulated fat metabolism in obese men at rest. METHOD: Twenty-three obese, healthy subjects were randomly divided in a low-intensity exercise training program (40% VO(2max), n=7), a high-intensity exercise training program (70% VO(2max); n=8), or a non-exercising control group (n=8). The exercise training program lasted for 12 weeks with a training frequency of 3 times per week. Before and after the intervention body composition and maximal aerobic capacity were measured as well as fat metabolism at rest and during beta-adrenergic stimulation by isoprenaline. For comparison, six lean subjects served as a control group. They participated in a low-intensity exercise training program and underwent the same measurements as the obese subjects. RESULTS: Relative fat oxidation decreased significantly during infusion of an increasing dose of isoprenaline in the obese low-intensity and high-intensity exercise training groups as well as in the lean group (P<0.01). Exercise training failed to influence the effect of beta-adrenergic stimulation on relative fat oxidation in obese men at both intensities and in lean men. In addition, beta-adrenergic-mediated lipolysis did not seem to be different after low intensity exercise training in lean and obese men. Lipolysis might be increased after high-intensity exercise training in obese men. CONCLUSION: Low- and high-intensity exercise training in obese men failed to affect beta-adrenergic mediated relative fat oxidation in vivo. beta-Adrenergic-mediated lipolysis might be increased in obese men after HI exercise training only. The effect of low-intensity exercise training on beta-adrenergic-mediated fat metabolism was similar in lean and obese men. International Journal of Obesity (2001) 25, 16-23

Determinants of the acetate recovery factor: implications for estimation of [13C]substrate oxidation.

When using (13)C or (14)C tracers to study substrate metabolism, an acetate correction factor should be applied to correct for loss of label in the exchange pathways of the tricarboxylic acid cycle. We have shown recently that the [(13)C]acetate recovery factor has a high inter-individual variability and should therefore be determined in every subject. In the present study we examined the factors that might explain some of the variability between subjects in acetate recovery factor. Data were pooled from four different studies with identical protocols, in which the acetate recovery factor was measured, prior to an intervention, to correct plasma fatty acid oxidation rates. Acetate recovery was measured after 2 h of [1, 2-(13)C]acetate infusion at rest followed by 1 h of cycling exercise at 40-50% of maximal oxygen uptake. Inter-individual variance in acetate recovery was 12.0% at rest and 16.1% during exercise. Stepwise regression revealed that, at rest, 37.1% of the acetate recovery could be accounted for by basal metabolic rate adjusted for fat-free mass, percentage body fat and respiratory quotient (RQ). During exercise, 69.1% of the variance in acetate recovery could be accounted for by energy expenditure adjusted for fat-free mass, % body fat and RQ. In conclusion, we show that the acetate recovery factor has a high inter-individual variability, both at rest and during exercise, which can partly be accounted for by metabolic rate, RQ and % body fat. These data indicate that the acetate recovery factor needs to be determined in every subject, under similar conditions as used for the tracer-derived determination of substrate oxidation. Failure to do this might result in large under- or over-estimation of plasma substrate oxidation, and hence to artificial differences between groups.

The effect of low-intensity exercise training on fat metabolism of obese women.

OBJECTIVE: Previous studies have shown that fat metabolism is different in upper body (UB) and lower body (LB) obese women. The present study investigated whether the effect of low-intensity exercise training on fat metabolism is different in UB and LB obese premenopausal women. RESEARCH METHODS AND PROCEDURES: Twenty-one healthy, premenopausal women with either LB obesity (waist-to-hip ratio of < or =0.79; n = 8) or UB obesity (waist-to-hip ratio of > or =0.85; n = 13) participated in the present study. The UB obese women were matched and randomly divided in an exercise training group (UB) and a nonexercising control group (UB-C). Subjects in the UB and LB groups participated in a low-intensity exercise training program (40% VO2max) three times per week for 12 weeks. Before and after the intervention, measurements of fat metabolism at rest and during exercise, body composition, and maximal aerobic capacity were performed. RESULTS: Exercise training did not change the respiratory exchange ratio at rest in the UB and LB groups. During exercise, relative fat oxidation increased in the UB group by 19% (p < 0.05), whereas no change in the LB and UB-C groups was found. Plasma free fatty acid oxidation did not change by exercise training, and nonplasma fatty acid oxidation tended to increase in the UB group compared with the UB-C group (p = 0.08). DISCUSSION: Low-intensity exercise training increased the contribution of fat oxidation to total energy expenditure during exercise but not at rest in UB obese women. Exercise training had no significant effect on fat metabolism in the LB obese women.

Regulation of average 24h human plasma leptin level; the influence of exercise and physiological changes in energy balance.

OBJECTIVE: The effects of short-term moderate physiological changes in energy flux and energy balance, by exercise and over- or underfeeding, on a 24h plasma leptin profile, were investigated. DESIGN: Subjects were studied over 24h in four randomized conditions: no exercise/energy balance (energy intake (EI)=energy expenditure (EE)=11.8+/-0.8 MJ); exercise/energy balance (EI=EE=15.1+/-0.6 MJ); exercise/negative energy balance (EI=11.8+/-0.8 MJ, EE=15.1+/-0.8 MJ); exercise/positive energy balance (El=18.6+/-0.7 MJ, EE=15.1+/-0.6 MJ). SUBJECTS: Eight healthy, lean men (age: 23.5+/-7.0y, body fat 14.1+/-5.4%, body mass index (BMI): 21.4+/-2.3 kg/m2). MEASUREMENTS: Blood was sampled every hour during the daytime (09.00-23.00h) and every two hours during the night (01.00-09.00h) for analysis of plasma leptin, insulin, glucose, FFA and catecholamines. RESULTS: Plasma leptin levels were highest around 01.00h (mean+/-s.e.m. 4.9+/-2.0 ng/ml) and lowest around 11.00 h. (2.3+/-0.7 ng/ml). An increased 24h EE, induced by exercise under conditions of energy balance, significantly decreased the peak and average 24h plasma leptin concentration. A positive energy balance, by overfeeding, resulted in a significantly higher amplitude of the 24h plasma leptin curve, compared to a condition of energy balance. CONCLUSION: Exercise decreases peak and average 24h plasma leptin concentration and a moderately positive energy balance increases the amplitude of the 24h plasma leptin profile. These effects are not acute, but are manifest within 24h. The variations of average 24h FFA and average 24h glucose concentrations almost fully explained the variation in average 24h leptin concentration across trials.

Validation of the [1,2-13C]acetate recovery factor for correction of [U-13C]palmitate oxidation rates in humans.

1. The validity of estimations of plasma fatty acid oxidation using tracers has often been questioned. The appearance of isotopic markers in breath CO2 is delayed and incomplete. Recently suggestions have been made that substantial amounts of tracer are incorporated into products of the tricarboxylic acid cycle (e.g. glucose, glutamine and glutamate) and that an acetate correction factor can be used to correct for tracer fixation. In the present study we investigated whether the appearance of 13CO2 during a separate infusion of [1,2-13C]acetate could be used for correction of [U-13C]palmitate oxidation rates in studies lasting <2 h and we quantified the appearance of tracer in the glutamine, glutamate and glucose pools of the body. 2. An infusion of either [1,2-13C]acetate (0.104 micromol min-1 kg-1) or [U-13C]palmitate (0.013 micromol min-1 kg-1) was given to eight male subjects and continued for 2 h at rest. In six subjects the infusion of [1,2-13C]acetate was repeated to determine reproducibility of the acetate recovery. 3. Fractional recovery in breath from [1,2-13C]acetate gradually increased during the infusion period at rest from 14.1 +/- 0.6% at 60 min to 26.5 +/- 0.5% at 120 min after the start of the infusion. Intersubject coefficient of variance was 8.3 +/- 0.6% and intrasubject coefficient of variance of the acetate recovery tests was 4.0 +/- 1.5%. After 2 h of [1,2-13C]acetate infusion, 12.4 +/- 0.8 and 10.3 +/- 0.9% of infused 13C was incorporated in the glutamine and glutamate pools, respectively. 4. In conclusion, the [1,2-13C]acetate recovery factor can be used for correcting the rate of [U-13C]palmitate oxidation in infusing studies of 2 h in resting conditions. Failure to use this recovery factor leads to a substantial underestimation of the rate of plasma free fatty acid oxidation. The extent of label fixation could largely be explained by accumulation of tracer carbon in glutamine and glutamate, and the accumulation in glucose is negligible.