A mathematical model to describe fat oxidation kinetics during graded exercise.

PURPOSE: The purpose of this study was to develop a mathematical model (sine model, SIN) to describe fat oxidation kinetics as a function of the relative exercise intensity [% of maximal oxygen uptake (%VO2max)] during graded exercise and to determine the exercise intensity (Fatmax) that elicits maximal fat oxidation (MFO) and the intensity at which the fat oxidation becomes negligible (Fatmin). This model included three independent variables (dilatation, symmetry, and translation) that incorporated primary expected modulations of the curve because of training level or body composition. METHODS: Thirty-two healthy volunteers (17 women and 15 men) performed a graded exercise test on a cycle ergometer, with 3-min stages and 20-W increments. Substrate oxidation rates were determined using indirect calorimetry. SIN was compared with measured values (MV) and with other methods currently used [i.e., the RER method (MRER) and third polynomial curves (P3)]. RESULTS: There was no significant difference in the fitting accuracy between SIN and P3 (P = 0.157), whereas MRER was less precise than SIN (P < 0.001). Fatmax (44 +/- 10% VO2max) and MFO (0.37 +/- 0.16 g x min(-1)) determined using SIN were significantly correlated with MV, P3, and MRER (P < 0.001). The variable of dilatation was correlated with Fatmax, Fatmin, and MFO (r = 0.79, r = 0.67, and r = 0.60, respectively, P < 0.001). CONCLUSIONS: The SIN model presents the same precision as other methods currently used in the determination of Fatmax and MFO but in addition allows calculation of Fatmin. Moreover, the three independent variables are directly related to the main expected modulations of the fat oxidation curve. SIN, therefore, seems to be an appropriate tool in analyzing fat oxidation kinetics obtained during graded exercise.

Comparison of sweat rate during graded exercise and the local rate induced by pilocarpine

Centrally stimulated sweat rate produced by graded exercise until exhaustion was compared to the local sweat rate induced by pilocarpine, often used as a sweating index for healthy individuals. Nine young male volunteers (22 ± 4 years) were studied in temperate environment in two situations: at rest and during progressive exercise with 25 W increases every 2 min until exhaustion, on a cycle ergometer. In both situations, sweating was induced on the right forearm with 5 ml 0.5% pilocarpine hydrochloride applied by iontophoresis (1.5 mA, 5 min), with left forearm used as control. Local sweat rate was measured for 15 min at rest. During exercise, whole-body sweat rate was calculated from the body weight variation. Local sweat rate was measured from the time when heart rate reached 150 bpm until exhaustion and was collected using absorbent filter paper. Pharmacologically induced local sweat rate at rest (0.4 ± 0.2 mg cm-2 min-1) and mean exercise-induced whole-body sweat rate (0.4 ± 0.1 mg cm-2 min-1) were the same (P > 0.05) but were about five times smaller than local exercise-induced sweat rate (control = 2.1 ± 1.4; pilocarpine = 2.7 ± 1.2 mg cm-2 min-1), indicating different sudorific mechanisms. Both exercise-induced whole-body sweat rate (P < 0.05) and local sweat rate (P < 0.05) on control forearm correlated positively with pilocarpine-induced local sweat rate at rest. Assuming that exercise-induced sweating was a result of integrated physiological mechanisms, we suggest that local and whole-body sweat rate measured during graded exercise could be a better sweating index than pilocarpine.

Evaluation of the best-designed graded exercise test to assess peak treadmill speed

This study examined the influence of different speed increments during treadmill exercise tests on peak treadmill speed (Vpeak) and its relationship with a 1-h treadmill running performance. 18 male recreational and amateur runners (10-km running pace: 10–15 km·h−1) performed, in an alternate order, 3 continuous incremental exercise tests with different speed increments (0.5, 1.0 and 2.0 km·h−1) on a motorized treadmill to determine Vpeak. Thereafter they undertook a 1-h time trial on a treadmill. Vpeak was determined as either (a) the highest speed that could be maintained for a complete minute (Vpeak-60 s), (b) the speed of the last complete stage (Vpeak-C), or (c) the speed of the last complete stage added to the product of the speed increment and the completed fraction of the incomplete stage (Vpeak-P). The Vpeak values were highly influenced by the different speed-incremented rates and the Vpeak-P determined during the protocol comprising speed increments of 1 km·h−1 presented the highest correlation with 1-h time trial performance (r=0.89). The results suggest that a protocol with speed increments comprising 1 km·h−1 and with a 3-min stage duration should be used as standard for the determination of Vpeak to assess aerobic fitness and predict endurance performance in recreational runners. Furthermore, the Vpeak-P should be used for the determination of Vpeak.

Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE: The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO2) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease. METHODS: Thirty-seven patients (59.7 +/- 1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption. RESULTS: After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.49; PETCO(2)VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.39; PETCO(2)VAT and ventilatory efficiency r = -0.45). CONCLUSIONS: Both exercise training modalities showed similar increases in PETCO2 levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.

Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective: While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice.

Weight loss associated with exercise training restores ventilatory efficiency in obese children

The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10 +/- 0.2 years; BMI > 95(th) percentile) were randomly divided into two Study groups: D (n=17; BMI = 30 +/- 1 kg/m(2)) and DET (n = 21; 28 +/- 1 kg/m(2)). Ten lean children were included in a control group (10 +/- 0.3 years; 17 +/- 0.5 kg/m(2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO(2) peak). VentE was determined by the VE/VCO(2) method at VAT. Obese children showed lower VO(2) peak and lower VentE than controls (p < 0.05). After interventions, all obese children reduced body weight (p < 0.05). D group did not improve in terms of VO(2) peak or VentE (p > 0.05). In contrast, the DET group showed increased VO(2) peak (p = 0.01) and improved VentE(Delta VE/VCO(2) = -6.1 +/- 0.9; p = 0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.

Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.

CONTEXT: Sarcopenia is thought to be associated with mitochondrial (Mito) loss. It is unclear whether the decrease in Mito content is consequent to aging per se or to decreased physical activity. OBJECTIVES: The objective of the study was to examine the influence of fitness on Mito content and function and to assess whether exercise could improve Mito function in older adults. DESIGN AND SUBJECTS: Three distinct studies were conducted: 1) a cross-sectional observation comparing Mito content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults and sedentary (S) subjects matched for age and gender; and 3) a 4-month exercise intervention in S. SETTING: The study was conducted at a university-based clinical research center. OUTCOMES: Mito volume density (MitoVd) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins by Western blotting, mRNAs for transcription factors involved in M biogenesis by quantitative RT-PCR, and in vivo oxidative capacity (ATPmax) by (31)P-magnetice resonance spectroscopy. Peak oxygen uptake was measured by graded exercise test. RESULTS: Peak oxygen uptake was strongly correlated with MitoVd in 80 60- to 80-year-old adults. Comparison of chronically endurance-trained older adults vs S revealed differences in MitoVd, ATPmax, and some electron transport chain protein complexes. Finally, exercise intervention confirmed that S subjects are able to recover MitoVd, ATPmax, and specific transcription factors. CONCLUSIONS: These data suggest the following: 1) aging per se is not the primary culprit leading to Mito dysfunction; 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle Mito content and may prevent aging muscle comorbidities; and 3) the improvement of Mito function is all about content.

Moderate exercise blunts oxidative stress induced by normobaric hypoxic confinement

PURPOSE: Both acute hypoxia and physical exercise are known to increase oxidative stress. This randomized prospective trial investigated whether the addition of moderate exercise can alter oxidative stress induced by continuous hypoxic exposure. METHODS: Fourteen male participants were confined to 10-d continuous normobaric hypoxia (FIO2 = 0.139 +/- 0.003, PIO2 = 88.2 +/- 0.6 mm Hg, approximately 4000-m simulated altitude) either with (HCE, n = 8, two training sessions per day at 50% of hypoxic maximal aerobic power) or without exercise (HCS, n = 6). Plasma levels of oxidative stress markers (advanced oxidation protein products [AOPP], nitrotyrosine, and malondialdehyde), antioxidant markers (ferric-reducing antioxidant power, superoxide dismutase, glutathione peroxidase, and catalase), nitric oxide end-products, and erythropoietin were measured before the exposure (Pre), after the first 24 h of exposure (D1), after the exposure (Post) and after the 24-h reoxygenation (Post + 1). In addition, graded exercise test in hypoxia was performed before and after the protocol. RESULTS: Maximal aerobic power increased after the protocol in HCE only (+6.8%, P < 0.05). Compared with baseline, AOPP was higher at Post + 1 (+28%, P < 0.05) and nitrotyrosine at Post (+81%, P < 0.05) in HCS only. Superoxide dismutase (+30%, P < 0.05) and catalase (+53%, P < 0.05) increased at Post in HCE only. Higher levels of ferric-reducing antioxidant power (+41%, P < 0.05) at Post and lower levels of AOPP (-47%, P < 0.01) at Post + 1 were measured in HCE versus HCS. Glutathione peroxidase (+31%, P < 0.01) increased in both groups at Post + 1. Similar erythropoietin kinetics was noted in both groups with an increase at D1 (+143%, P < 0.01), a return to baseline at Post, and a decrease at Post + 1 (-56%, P < 0.05). CONCLUSIONS: These data provide evidence that 2 h of moderate daily exercise training can attenuate the oxidative stress induced by continuous hypoxic exposure.

Fat oxidation kinetics : effect of exercise

ABSTRACT Fat oxidation kinetics: effect of exercise. During graded exercise, absolute whole body fat oxidation rates increase from low to moderate intensities, and then markedly decline at high intensities, implying an exercise intensity (Fatmax) at which the fat oxidation rate is maximal (MFO). The main aim of the present work was to examine the effect of exercise on whole body fat oxidation kinetics. For this purpose, a sinusoidal mathematical model (SIN) has been developped in the first study to provide an accurate description of the shape of fat oxidation kinetics during graded exercise, represented as a function of exercise intensity, and to determine Fatmax and MFO. The SIN model incorporates three independent variables (i.e., dilatation, symmetry, and translation) that correspond to main expected modulations of the basic fat oxidation curve because of factors such as mode of exercise or training status. The results of study 1 showed that the SIN model was a valuable tool to determine Fatmax and MFO, and to precisely characterize and quantify the different shape of fat oxidation kinetics through its three variables. The effectiveness of the SIN model to detect differences in fat oxidation kinetics induced by a specific factor was then confirmed in the second study, which quantitatively described and compared fat oxidation kinetics in two different popular modes of exercise: running and cycling. It was found that the mean fat oxidation kinetics during running was characterized by a greater dilatation and a rightward asymmetry compared with the symmetric parabolic curve in cycling. In the two subsequent studies, the effect of a prior endurance exercise of different intensities and durations on whole body fat oxidation kinetics was examined. Study 3 determined the impact of a 1-h continuous exercise bout at an exercise intensity corresponding to Fatmax on fat oxidation kinetics during a subsequent graded test, while study 4 investigated the effect of an exercise leading to a more pronounced muscle glycogen depletion. The results of these two latter studies showed that fat oxidation rates, MFO, and Fatmax were enhanced following endurance exercise, but were increased to a greater extent with a more severe mucle glycogen depletion, inducing therefore modifications in the postexercise fat oxidation kinetics (i.e., greater dilatation and rightward asymmetry). In perspective, further studies have been suggested 1) to assess physiological meaning of the three independent variables of the SIN model; and 2) to compare the effect of two different training programs on fat oxidation kinetics in obese subjects.

Gender differences in whole body fat oxidation kinetics during exercise

Introduction Discrepancies appear in studies comparing fat oxidation between men and women during exercise (1). Therefore, this study aimed to quantitatively describe and compare whole body fat oxidation kinetics between genders during exercise using a sinusoidal model (SIN) (2). Methods Twelve men and 11 women matched for age, body mass index (23.4±0.6 kg.m-2 and 21.5±0.8 kg.m-2, respectively) and aerobic fitness [maximal oxygen uptake ( ) (58.5±1.6 mL.kg FFM-1.min-1 and 55.3±2.0 mL.kg FFM-1.min-1, respectively) and power output ( ) per kilogram of fat-free mass (FFM)] performed submaximal incremental tests (Incr) with 5-min stages and 7.5% increment on a cycle ergometer. Respiratory and HR values were averaged over the last 2 minutes of each stage. All female study participants were eumenorrheic, reported regular menstrual cycles (28.6 ± 0.8 days) and were not taking oral contraceptives (OC) or other forms of exogenous ovarian hormones. Women were studied in the early follicular phase (FP) of their menstrual cycle (between days 3 and 8, where day 1 is the first day of menses). Fat oxidation rates were determined using indirect calorimetry and plotted as a function of exercise intensity. The SIN model (2), which includes three independent variables (dilatation, symmetry, translation), was used to mathematically describe fat oxidation kinetics and to determine the intensity (Fatmax) eliciting the maximal fat oxidation (MFO). Results During Incr, women exhibited greater fat oxidation rates from 35 to 85% , MFO (6.6 ± 0.9 vs. 4.5 ± 0.3 mgkg FFM-1min-1) and Fatmax (58.1 ± 1.9 vs. 50.0 ± 2.7% ) (P<0.05) than men. While men and women showed similar global shapes of fat oxidation kinetics in terms of dilatation and symmetry (P>0.05), the fat oxidation curve tended to be shifted towards higher exercise intensities in women (rightward translation, P=0.08). Conclusion These results showed that women, eumenorrheic, not taking OC and tested in FP, have a greater reliance on fat oxidation than men during submaximal exercise, but they also indicate that this greater fat oxidation is shifted towards higher exercise intensities in women compared with men. References 1. Blaak E. Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care 4: 499-502, 2001. 2. Cheneviere X, Malatesta D, Peters EM, and Borrani F. A mathematical model to describe fat oxidation kinetics during graded exercise. Med Sci Sports Exerc 41: 1615-1625, 2009.

Exercise dose and insulin sensitivity: relevance for diabetes prevention.

PURPOSE: Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults. METHODS: Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency. RESULTS: Improved insulin sensitivity was significantly related to exercise dose in a graded dose-response relationship. No evidence of threshold or maximal dose-response effect was observed. Age and gender did not influence this dose-response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not. CONCLUSIONS: This study identifies a graded dose-response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations.

Postprandial thermogenesis at rest and during exercise in elderly men ingesting two levels of protein.

Seven elderly male subjects (69 +/- 3 yr, 67.8 +/- 9.2 kg, 24.5 +/- 3.6% body fat) lived for 12 consecutive weeks in a metabolic unit and maintained their weight with two different diets fed for 6 weeks each: Diet A, consisted of their habitual protein intake as determined on the outside by a dietary record (mean +/- SD, 1.12 +/- 0.22 g/kg d). Diet B was an isocaloric diet with reduced protein intake (70 mgN/kg d, i.e., 0.44 g protein/kg d) at the level of physiological protein requirement [7]. After 3 weeks on each diet, the thermogenic response to single meals A and B containing 38% of weight maintenance energy for each subject (731-994 kcal) was studied by indirect calorimetry under two situations: (1) at rest over a 4 hr period and (2) during graded exercise on a bicycle ergometer at four stepwise workloads (0,80, 200, and 300 kg/min). A postabsorptive control exercise was also performed in order to assess the net effect of the meal during exercise. Eating alone increased the energy expenditure by +0.18 +/- 0.07 kcal/min with meal A and +0.13 +/- 0.06 kcal/min with meal B. There was a positive correlation (r = 0.84, p less than 0.01) between the % energy derived from protein and the thermogenic response expressed as % of the energy content of test meal. Exercise failed to influence the thermogenic response to meals since the overall net increase in energy expenditure induced by the meals while exercising was not different from that obtained at rest: +0.22 +/- 0.17 kcal/min and +0.15 +/- 0.13 kcal/min with meal A and meal B, respectively. This study failed to show any interaction between exercise and postprandial thermogenesis in elderly individuals.

Exercise efficiency relates with mitochondrial content and function in older adults.

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty-eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1-h submaximal test (55% V˙O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with (31)P-MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Fat oxidation over a range of exercise intensities: fitness versus fatness.

Maximal fat oxidation (MFO), as well as the exercise intensity at which it occurs (Fatmax), have been reported as lower in sedentary overweight individuals but have not been studied in trained overweight individuals. The aim of this study was to compare Fatmax and MFO in lean and overweight recreationally trained males matched for cardiorespiratory fitness (CRF) and to study the relationships between these variables, anthropometric characteristics, and CRF. Twelve recreationally trained overweight (high fatness (HiFat) group, 30.0% ± 5.3% body fat) and 12 lean males (low fatness (LoFat), 17.2% ± 5.7% body fat) matched for CRF (maximal oxygen consumption (V̇O2max) 39.0 ± 5.5 vs. 41.4 ± 7.6 mL·kg(-1)·min(-1), p = 0.31) and age (p = 0.93) performed a graded exercise test on a cycle ergometer. V̇O2max and fat and carbohydrate oxidation rates were determined using indirect calorimetry; Fatmax and MFO were determined with a mathematical model (SIN); and % body fat was assessed by air displacement plethysmography. MFO (0.38 ± 0.19 vs. 0.42 ± 0.16 g·min(-1), p = 0.58), Fatmax (46.7% ± 8.6% vs. 45.4% ± 7.2% V̇O2max, p = 0.71), and fat oxidation rates over a wide range of exercise intensities were not significantly different (p > 0.05) between HiFat and LoFat groups. In the overall cohort (n = 24), MFO and Fatmax were correlated with V̇O2max (r = 0.46, p = 0.02; r = 0.61, p = 0.002) but not with % body fat or body mass index (p > 0.05). Fat oxidation during exercise was similar in recreationally trained overweight and lean males matched for CRF. Consistently, substrate oxidation rates during exercise were not related to adiposity (% body fat) but were related to CRF. The benefits of high CRF independent of body weight and % body fat should be further highlighted in the management of obesity.