Neuregulin 1 affects leptin levels, food intake and weight gain in normal-weight, but not obese, db/db mice.

AIM: Studies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice. METHODS: Weight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50 µg/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks. RESULTS: Leptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment. CONCLUSION: The decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

Overweight after deep brain stimulation of the subthalamic nucleus in Parkinson disease: long term follow-up.

OBJECTIVE: To assess the occurrence of weight gain in patients with Parkinson's disease, with an average 16 months of follow-up after subthalamic nucleus deep brain stimulation. METHODS: We used dual x ray absorptiometry to evaluate changes in body weight and body composition in 22 patients with Parkinson's disease (15 men and seven women) before surgery, 3 months after surgery and on average 16 months after surgery. RESULTS: No patient was underweight before surgery and 50% were overweight. By contrast, 68% were overweight or obese 3 months after surgery and 82% after 16 months (p<0.001). For men, the mean increase in body mass index (BMI) was 1.14 (0.23) kg/m(2) 3 months after surgery and 2.02 (0.36) kg/m(2) 16 months after surgery. For women, the mean increases in BMI at the same evaluation times were 1.04 (0.30) kg/m(2) and 2.11 (0.49) kg/m(2). This weight gain was mainly secondary to an increase in fat mass in both men and women. Three months after surgery, acute subthalamic deep brain stimulation induced an improvement in parkinsonian symptoms (evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III) by 60.7 (2.9)% in the "off" dopa condition and a dramatic improvement of motor complications (dyskinesia duration: 82.8 (12.8)%, p<0.0001; off period duration: 92.7 (18.8)%, p<0.0001). CONCLUSION: Although subthalamic nucleus deep brain stimulation significantly improved parkinsonian symptoms and motor complications, many patients became overweight or obese. This finding highlights the necessity to understand the underlying mechanisms and to provide a diet management with a physical training schedule appropriate for patients with Parkinson's disease.

Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation.

Chronic bilateral subthalamic stimulation leads to a spectacular clinical improvement in patients with motor complications. However, the post-operative body weight gain involved may limit the benefits of surgery and induce critical metabolic disorders. Twenty-four Parkinsonians (61.1 +/- 1.4 years) were examined 1 month before (M - 1) and 3 months after (M + 3) surgery. Body composition and energy expenditure (EE) were measured (1) over 36 h in calorimetric chambers (CC) with rigorous control of food intakes and activities [sleep metabolic rate, resting activities, meals, 3 or 4 sessions of 20 min on a training bicycle at 13 km/h and daily EE] and (2) in resting conditions (basal metabolic rate) during an acute L-dopa challenge (M - 1) or according to acute 'off' and 'on' stimulation (M + 3). Before surgery, EE was compared between the Parkinsonian patients and healthy subjects matched for height and body composition (metabolic rate during sleep, daily EE) or matched to predicted values (basal metabolic rate). Before surgery, in Parkinsonian men but not women, (1) daily EE was higher while sleep metabolic rate was lower compared to healthy matched men (+9.2 +/- 3.9 and -8.2 +/- 2.3%, respectively, P < 0.05) and (2) basal metabolic rate (L-dopa 'on') was higher than predicted basal metabolic rate (+11.5 +/- 4.0%, P < 0.05) but was further increased without L-dopa (+8.4 +/- 3.2% vs L-dopa 'on', P < 0.05). EE during daily activities was higher during 'off' periods compared to 'on' periods for both men (+19.3 +/- 3.3%, P < 0.0001) and women (+16.1 +/- 4.7%, P < 0.01). After surgery, there was a 3.4 +/- 0.6 kg (P < 0.0001) body weight increase together with fat mass (P < 0.0001) and fat-free mass (P < 0.05) in Parkinsonian men and a 2.6 +/- 0.8 kg (P < 0.05) body weight increase together with fat mass (P < 0.05) in Parkinsonian women. Sleep metabolic rate increased in men (+7.5 +/- 2.0%, P < 0.01) to reach control values but remained unchanged in women. Daily EE decreased significantly in both men and women (-7.3 +/- 2.2% and -13.1 +/- 1.7%, respectively, P < 0.01) but there was no correlation between daily EE changes and body weight gain. Parkinson's disease is associated with profound alterations in the central control of energy metabolism. Normalization of energy metabolism after DBS-STN implantation may favour body weight gain, of which quality was gender specific. As men gained primarily fat-free mass, a reasonable weight gain may be tolerated, in contrast with women who gained only fat. Other factors such as changes in free-living physical activity may help to limit body weight gain in some patients.

Behavioral and physiological regulation of body fatness: a cross-sectional study in elderly men.

OBJECTIVE: To identify the characteristics of physical activity that are the most correlated to total and truncal fatness and to physiological parameters involved in fat oxidation in elderly men. DESIGN: Cross-sectional study. SUBJECTS: A total of 25 healthy elderly men selected with a wide range of physical activity behavior (65.9 +/- 3.4 years). MEASUREMENTS: Total and truncal fat masses (by dual-energy X-ray absorptiometry), time spent and energy expended (EE(day)) at specific activity intensities (<40, 40-60, >60% VO2max) during 1 week in free living conditions (using heart rate recording and individual calibrated equations), sport-exercising volume (V(sport), using Baecke questionnaire), maximal oxygen uptake (VO2max), muscle fat oxidative capacity (OX(FA), using muscle biopsy), lipid oxidation and respiratory exchange ratio during exercise at 50% VO2max (using indirect calorimetry). RESULTS: V(sport) was the main determinant of total and truncal fatness, VO2max and OX(FA) (r = -0.69, P < 0.0001; r = -0.80, P < 0.0001; r = 0.70, P < 0.0001; r = 0.66, P<0.001, respectively). Among physical activity parameters measured over a week, total EE(day) was the main determinant of total fat mass. Furthermore, EE(day) at % VO2max > 60 was closely correlated to truncal fat mass, VO2max and OX(FA) (r = -0.58, P > 0.01; r = 0.55, P < 0.01; r = 0.49, P < 0.05, respectively). Finally, VO2max and OX(FA) were positively correlated to absolute fat oxidation and to the contribution of fat to energy production during moderate exercise. CONCLUSION: Sport-exercising volume is the main factor regulating total and truncal fat masses and physiological parameters involved in fat oxidation. With regard to the characteristics of physical activity, overall energy expended during the alert period plays a major role in the regulation of total body fatness. In addition, vigorous exercises may be beneficial for the regulation of abdominal fat depot partly through the stimulation of muscle fat oxidation during the effort.

Changes in adipocyte hormones and lipid oxidation associated with weight loss and regain in severely obese adolescents.

OBJECTIVE: To investigate changes in adipocyte hormones and lipid oxidation during and after a weight-reduction programme in severely obese adolescents. DESIGN: Longitudinal-clinical investigation including a 9-month multidisciplinary weight-reduction programme in a specialised institution with lifestyle education, moderate energy restriction and regular physical activity, followed by a 4-month period at home. SUBJECTS: A total of 26 (12 boys and 14 girls) severely obese adolescents (mean BMI: 33.9 kg/m2; 41.5% fat mass (FM)). MEASUREMENTS: Before starting (M0), at the end (M9), and 4 months after the end (M13) of the intervention blood samples were collected at fast, body composition was assessed by dual X-ray absorptiometry, and energy expenditure (EE) and substrate oxidation were assessed by whole-body indirect calorimetry over 24 h. RESULTS: At M9, adolescents had lost 19.0% body weight (BW), 41.3% FM (P<0.001), with a minor fat free mass (FFM) loss in girls (6.4%, P<0.001) but no significant FFM changes in boys. Plasma leptin concentration at M9 was 70% lower (P<0.001), whereas plasma adiponectin concentration was 26.6% higher (P<0.001). The results also suggest that after adjustment for FFM and energy balance, sleeping and sedentary activity lipid oxidation rates were higher at M9 than at M0. At M13, plasma adiponectin, insulin, glucose and LDL concentrations returned to the initial levels, and leptin to an intermediate level in the 10 adolescents who had regained BW. Adjusted lipid oxidation rate decreased in both groups of subjects but it was not correlated to any change in plasma adipocyte hormones, which rather changed in relation to FM modifications. CONCLUSION: Moderate energy restriction and regular moderate and high intensity physical activities in obese adolescents induced beneficial changes in BW and composition, lipid oxidation and blood parameters, especially adipocyte hormones.

Energy value of a low-digestible carbohydrate, NUTRIOSE FB, and its impact on magnesium, calcium and zinc apparent absorption and retention in healthy young men.

BACKGROUND: Long-term consumption of imbalanced diets, poor in dietary fibres, resulted in the prevalence of several nutritional pathologies. However, low digestible carbohydrates (LDC) have many beneficial effects, especially on energy intake, digestive physiology, and mineral absorption. AIM OF THE STUDY: To determine the digestive effects of a LDC, called NUTRIOSE FB, its metabolisable energy (ME) value, and its effects on mineral absorption in humans. METHODS: Ten healthy young men were fed for 31 d periods a maintenance diet supplemented with either dextrose or the LDC at a level of 100 g DM/d, in six equal doses per d according to a cross-over design. After a 20 d adaptation period, food intake was determined for 11 days using the duplicate meal method, and faeces and urine were collected for 10 d for further analyses. RESULTS: Ingestion of the LDC did not cause severe digestive disorders, except excessive gas emission, and flatulence and slight abdominal pain in some subjects for intakes above 50 g DM/d. Wet and dry stool outputs increased by 45 and 70%, respectively (P<0.02). In vitro enzymatic digestibility of the LDC was 15 (SD 1.5) %, and 9.2 (SD 8.3) % of the LDC was excreted in faeces (P<0.001). The ME value of the LDC was 14.1 (SD 2.3) kJ/g DM, that is 14 % less than the tabulated values of sucrose and starch. Its net energy value (NEV), estimated using three prediction equations, was 8.7, 8.9, and 11.4 kJ/g DM. Ingestion of the LDC significantly increased the relative apparent absorption of Mg, and Mg retention by 67% and 31 mg/d, respectively, tended to increase Ca apparent absorption (P=0.110) and Ca retention (P=0.059), but did not significantly alter Zn parameters. CONCLUSION: NUTRIOSE FB can be used as a "bulking" agent, and substituted up to 50 g/d for usual maltodextrins without causing digestive disorders in healthy subjects. It would reduce intestinal transit disorders and energy intake, and improve magnesium and calcium absorption and retention.

Reduced whole-body fat oxidation in women and in the elderly.

OBJECTIVE: To test the hypothesis that the increase in fat mass observed with aging might be related to a decrease in whole-body fat oxidation. SUBJECTS AND MEASUREMENTS: Forty volunteers had measurements of sleeping and 24 h substrate oxidation in calorimetric chambers, body composition with the (18)O dilution technique, VO(2)max, and fiber composition analysis from a biopsy of vastus lateralis. They were divided into 10 young women, 10 young men, 10 elderly women and 10 elderly men. RESULTS: Sleeping fat oxidation and 24 h fat oxidation were lower in women than in men and in elderly than in young participants. Sleeping fat oxidation was correlated to fat-free mass and energy balance (multivariate analysis). Twenty four hour fat oxidation was correlated to total energy expenditure and energy balance (multivariate analysis). After adjustment for differences in these factors, sleeping and 24 h fat oxidation were no longer different between age and sex groups. None of the parameters of macronutrient metabolism was correlated with muscle fiber composition. CONCLUSION: Our data suggest that fat oxidation is lower in elderly subjects. This difference could favour fat mass gain if fat intake is not adequately reduced. Differences in fat-free mass and in total energy expenditure appear to participate in the reduction in fat oxidation. International Journal of Obesity (2001) 25, 39-44

Muscle fatty acid oxidative capacity is a determinant of whole body fat oxidation in elderly people.

In sedentary elderly people, a reduced muscle fatty acid oxidative capacity (MFOC) may explain a decrease in whole body fat oxidation. Eleven sedentary and seven regularly exercising subjects (65.6 +/- 4. 5 yr) were characterized for their aerobic fitness [maximal O(2) uptake (VO(2 max))/kg fat free mass (FFM)] and their habitual daily physical activity level [free-living daily energy expenditure divided by sleeping metabolic rate (DEE(FLC)/SMR)]. MFOC was determined by incubating homogenates of vastus lateralis muscle with [1-(14)C]palmitate. Whole body fat oxidation was measured by indirect calorimetry over 24 h. MFOC was 40.4 +/- 14.7 and 44.3 +/- 16.3 nmol palmitate. g wet tissue(-1). min(-1) in the sedentary and regularly exercising individuals, respectively (P = nonsignificant). MFOC was positively correlated with DEE(FLC)/SMR (r = 0.58, P < 0. 05) but not with VO(2 max)/kg FFM (r = 0.35, P = nonsignificant). MFOC was the main determinant of fat oxidation during all time periods including physical activity. Indeed, MFOC explained 19.7 and 30.5% of the variance in fat oxidation during walking and during the alert period, respectively (P < 0.05). Furthermore, MFOC explained 23.0% of the variance in fat oxidation over 24 h (P < 0.05). It was concluded that, in elderly people, MFOC may be influenced more by overall daily physical activity than by regular exercising. MFOC is a major determinant of whole body fat oxidation during physical activities and, consequently, over 24 h.

Daily energy expenditure and its main components as measured by whole-body indirect calorimetry in athletic and non-athletic adolescents.

The objectives of the present study were to determine whether differences in usual physical activity affect BMR, sleeping energy expenditure (EE), and EE during seated activities between athletic and non-athletic adolescents, and to establish individual relationships between heart rate and EE. Adolescents (n 49, four groups of eleven to fifteen boys or girls aged 16-19 years) participated in the study. Body composition was measured by the skinfold-thickness method and maximum O2 consumption (VO2max) by a direct method (respiratory gas exchange) on a cycloergometer. The subjects each spent 36 h in one of two large whole-body calorimeters. They followed a standardized activity programme including two periods of exercise simulating their mean weekly physical activities. Fat-free mass (FFM), VO2max, daily EE and EE during sleep and seated activities were significantly higher in athletic than in non-athletic subjects of both sexes. VO2max, daily EE and EE during exercise adjusted for FFM were higher in athletic than in non-athletic adolescents (P < 0.001), whereas sleeping EE, BMR and EE during seated activities and adjusted for FFM were not significantly different between athletic and non-athletic adolescents. However, sex differences in EE remained significant. Thus, differences in EE between athletic and non-athletic adolescents resulted mainly from differences in FFM and physical exercise. Usual activity did not significantly affect energy utilization of substrates. Finally, individual relationships were computed between heart rate and EE with activity programmes simulating the usual activities of athletic and non-athletic adolescents with the goal of predicting EE of the same subjects in free-living conditions.

Time-course effects of endurance training on fat oxidation in sedentary elderly people.

OBJECTIVE: To investigate alterations in whole body fat oxidation after 7 and 14 weeks of progressive endurance training in sedentary elderly subjects. DESIGN: Longitudinal, 14 weeks of progressive endurance training on a cycle ergometer (3 training sessions per week). Full sets of measurements were performed before, and after 7 and 14 weeks of training. SUBJECTS: 13 healthy sedentary subjects (5 men, 8 women) (age 62.8 +/- 2.3 y). MEASUREMENTS: 24 h indirect calorimetric measurements under standardised conditions: light-activity programme, fixed food composition, neutral daily energy balance. Body composition (by isotope dilution and skinfold thicknesses). Maximal oxygen consumption. RESULTS: Loss of 0.7 kg fat mass in the first 7 weeks of training and a further 2.4 kg of fat in the second 7 weeks. There was a transient increase in sleeping fat oxidation after 7 weeks of training (+26.1%), associated with transient increase in daily fat oxidation (+/- 11.9%), but fat oxidation then returned to baseline values in the second 7 weeks. There was a correlation between within-subject changes in sleeping fat oxidation after 7 weeks of training and variations in FFM (r = 0.62, P = 0.02) and maximal oxygen consumption (r = -0.56, P < 0.05). CONCLUSION: In sedentary elderly subjects, progressive endurance training was associated with a transient increase in sleeping fat oxidation and daily fat oxidation. In free-living conditions, possible changes in daily fat oxidation may have induced a negative fat balance, as judged by fat mass loss.

Effects of 14 weeks of progressive endurance training on energy expenditure in elderly people.

Effects of progressive endurance training on energy expenditure (EE) were studied in thirteen elderly sedentary subjects (62.8 (SD 2.3) years) after 7 and 14 weeks of training. Daily EE (DEE) and energy cost of the various usual activities were measured over 48 h by whole-body indirect calorimetry. Free-living DEE (DEEFLC) was calculated from 7 d activity recordings and the energy costs of activities were measured in the calorimeters using the factorial method. DEEFLC did not vary significantly throughout the training period despite the additional energy cost of training sessions (0.60 (SD 0.15) MJ/d), because energy expended during free-living activities (EEACT) decreased by 4.8 (SD 7.1)% (P < 0.05) and 7.7 (SD 8.6)% (P < 0.01) after 7 and 14 weeks of training respectively. Measurements in the calorimeters showed that sleeping metabolic rate transiently increased by 4.6 (SD 3.2)% after 7 weeks of training (P < 0.001) and returned to its initial level after 14 weeks of training. BMR was 7.6 (SD 7.0)% (P < 0.01) and 4.1 (SD 6.1)% (P = NS) higher after 7 and 14 weeks of training respectively, than before training. Likewise, diet-induced thermogenesis increased from 3.7 (SD 2.5) to 7.2 (SD 2.8)% energy intake after 7 weeks of training (P < 0.05), and returned to its initial level after 14 weeks of training (4.2 (SD 2.6)% energy intake). Despite these changes, energy expended during activities and the corresponding DEE did not vary throughout the training period. It was concluded that: (1) DEEFLC remained constant throughout the training period due to a compensatory decrease in free-living EEACT; (2) progressive endurance training induced a transient increase in sleeping metabolic rate, BMR and diet-induced thermogenesis after 7 weeks which was not reflected in the energy expended during activities and DEE.

Critical evaluation of the factorial and heart-rate recording methods for the determination of energy expenditure of free-living elderly people.

The aim of the present study was to validate against the doubly-labelled water (DLW) technique the factorial method and the heart rate (HR) recording method for determining daily energy expenditure (DEE) of elderly people in free-living conditions. The two methods were first calibrated and validated in twelve healthy subjects (six males and six females; 70.1 (SD 2.7) years) from open-circuit whole-body indirect calorimetry measurements during three consecutive days and during 1 d respectively. Mean energy costs of the various usual activities were determined for each subject using the factorial method, and individual relationships were set up between HR and energy expenditure for the HR recording method. In free-living conditions, DEE was determined over the same period of time by the DLW, the factorial and the HR recording methods during 17, 14 and 4 d respectively. Mean free-living DEE values for men estimated using the DLW, the factorial and the HR recording methods were 12.8 (SD 3.1), 12.7 (SD 2.2) and 13.5 (SD 2.7) MJ/d respectively. Mean free-living DEE values for women were 9.6 (SD 0.8), 8.8 (SD 1.2) and 10.2 (SD 1.5) MJ/d respectively. No significant differences were found between the three methods for either sex, using the Bland & Altman (1986) test. Mean differences in DEE of men were -0.9 (SD 11.8) % between the factorial and DLW methods, and + 4.7 (SD 16.1) % between the HR recording and DLW methods. Similarly, in women, mean differences were -7.7 (SD 12.7) % between the factorial and DLW methods, and + 5.9 (SD 8.8) % between the HR recording and DLW methods. It was concluded that the factorial and the HR recording methods are satisfactory alternatives to the DLW method when considering the mean DEE of a group of subjects. Furthermore, mean energy costs of activities calculated in the present study using the factorial method were shown to be suitable for determining free-living DEE of elderly people when the reference value (i.e. sleeping metabolic rate) is accurately measured.

Gender differences in energy expended during activities and in daily energy expenditure of elderly people.

Gender effects on energy expended during light seated activities, walking, cycling, and sleep and their consequences on daily energy expenditure (EE) were examined in 11 men and 15 women aged 66.4 +/- 7.1 yr. Two open-circuit whole body calorimeters were used for EE measurements, except for cycling, during which EE was measured separately with the use of a face mask. Lean body mass (determined using H218O dilution method), fat mass, usual physical activity level, and activity intensity (e.g., walking speed and cycling power output) were taken as covariates in the analysis of EE variations before studying gender effects. Sleeping metabolic rate (SMR) and daily EE, adjusted for differences in all covariates, were 11.2 (P = 0.005) and 8.7% (P = 0.071) lower in women than in men, respectively. No gender-related differences were found in the various physical activity EEs above SMR (e.g., gross EE-SMR) [light seated activities (P = 0.790), walking (P = 0.263), and cycling (P = 0.287)] and daily physical activity EE above SMR (P = 0.587) after adjustment for differences in all covariates. Therefore, the lower adjusted daily EE of women could be related to their lower SMR, the most reliable criterion of whole body metabolic rate.