Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor gene.

AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild-type co-twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post-prandial energy expenditure. CONCLUSIONS: In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.

Effects of isoenergetic overfeeding of either carbohydrate or fat in young men.

Ten pairs of normal men were overfed by 5 MJ/d for 21 d with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects in each pair were requested to follow each other throughout the day to ensure similar physical activity and were otherwise allowed to maintain normal daily life. The increase in body weight, fat free mass and fat mass showed great variation, the mean increases being 1.5 kg, 0.6 kg and 0.9 kg respectively. No significant differences between the C- and F-group were observed. Heat production during sleep did not change during overfeeding. The RQ during sleep was 0.86 and 0.78 in the C- and F-group respectively. The accumulated faecal loss of energy, DM, carbohydrate and protein was significantly higher in the C- compared with the F-group (30, 44, 69 and 51% higher respectively), whereas the fat loss was the same in the two groups. N balance was not different between the C- and F-group and was positive. Fractional contribution from hepatic de novo lipogenesis, as measured by mass isotopomer distribution analysis after administration of [1-(13)C]acetate, was 0.20 and 0.03 in the C-group and the F-group respectively. Absolute hepatic de novo lipogenesis in the C-group was on average 211 g per 21 d. Whole-body de novo lipogenesis, as obtained by the difference between fat mass increase and dietary fat available for storage, was positive in six of the ten subjects in the C-group (mean 332 (SEM 191)g per 21 d). The change in plasma leptin concentration was positively correlated with the change in fat mass. Thus, fat storage during overfeeding of isoenergetic amounts of diets rich in carbohydrate or in fat was not significantly different, and carbohydrates seemed to be converted to fat by both hepatic and extrahepatic lipogenesis.

[Effects of excessive isocaloric intake of either carbohydrate or fat on body composition, fat mass, de novo lipogenesis and energy expenditure in normal young men]. / Virkninger af isokalorisk overindtagelse af kulhydrat eller fedt på legemsvaegt, fedtmasse, de novo lipogenese og energiomsaetning hos normale unge maend.

Ten pairs of normal young men were overfed by 5 MJ per day for 21 days with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects of a pair were requested to follow each other throughout the day to ensure similar physical activity. The increase in body weight and fat mass were not significantly different between the C- and the F-group. Heat production during sleep did not change during overfeeding. The accumulated faecal loss of energy, dry matter, carbohydrate and protein was significantly higher in the C- than in the F-group. Hepatic de novo lipogenesis was 212 g per 21 days in the C-group and was too low to be determined in the F-group. Whole body de novo lipogenesis was positive in six of the ten subjects in the C-group (mean: 332 g per 21 days). It is concluded that the increase in body weight and fat mass during overfeeding of isocaloric amounts of diets rich in carbohydrate or in fat was not significantly different, and that surplus of carbohydrate seemed to be converted to fat both by hepatic and extrahepatic de novo lipogenesis.

A fast responding combined direct and indirect calorimeter for human subjects.

The construction and performance of a 5.4 m3 combined direct and indirect calorimeter for human subjects is described. The calorimeter was constructed for studies on human subjects primarily undergoing fast alterations in heat production and heat losses, e.g. after a meal or during physical exercise. A heat sink and a heat substitution principle is used to measure sensible heat losses directly. Evaporative heat losses are determined by measuring water vapour input and output. Indirect calorimetry is performed by measuring output air flow and changes in gas composition of the air entering and leaving the calorimeter. The response times (90%) for sensible heat and evaporative heat were found to be 4 min and 34 min, respectively. Three alcohol combustion tests gave a recovery of CO2 and O2 in the range 92-97%. The recovery of water was found to be in the range 56-89%.

Organ weights in healthy and apparently healthy Danish infants.

The weights of brain, heart, liver, kidneys, spleen, lungs, and thymus were registered in 222 forensic autopsies of Danish infants aged 1 week to 0.99 year (137 males, 85 females), who prior to death were healthy or apparently healthy based on clinical evidence. Variability of organ weights was estimated, and the relationship between individual organ weights and age, body weight, and body length, and the sum of organ weights was evaluated in relation to age, body weight, and body length. No significant differences were found between males and females, and between the healthy and apparently healthy infants. There was a positive, significant correlation of the individual organ weights with age, body weight, and body length. It was most pronounced for the weight of the brain and least pronounced for the thymus. Am. J. Hum. Biol. 9:35-38 © 1997 Wiley-Liss, Inc.

Between-subjects variation in energy expenditure: estimation of the effect of variation in organ size.

The between-subjects variation in energy expenditure over 24 h at a fixed physical activity and corrected for differences in fat and fat-free mass has recently been determined to be 6-7%. New data on the variation between subjects of the weights of the brain, liver, kidneys, heart and spleen together with estimates of the energy expenditure of these organs were used to calculate the part of the between-subjects variation in energy expenditure at a fixed physical activity that is due to this variation alone. The results show that this variation is close to 5%. Thus, a very considerable part of the total between-subjects variation can be explained by differences in the composition of the fat-free mass.

Weights of brain, heart, liver, kidneys, and spleen in healthy and apparently healthy adult Danish subjects.

Based on a forensic material of 1,598 autopsies of Danish adults (1,086 males, 512 females ≥ 16 years of age), who prior to death were healthy or apparently healthy based on clinical evidence, the weights of brain, heart, liver, kidneys, and spleen were registered. The variability of organ weights was estimated. Relationships between organ weights and body size, and among organ weights were also evaluated. Males had larger organ weights than females. When organ weights were based on the same estimated fat free mass, interesting differences between the sexes were observed: weights of the heart and brain were smaller in females, but weights of the kidney were the same; weights of the liver were consistently larger in females than in males. Useful comparisons of the data with previous studies were impossible because of differences in the criteria of health and of insufficient numbers. © 1993 Wiley-Liss, Inc.

Within-subjects variation over 10 months in 24-hour energy expenditure at a fixed physical activity programme.

In order to estimate within-subjects variability in 24-hour energy expenditure at a fixed physical activity programme with a physical activity index of 1.30, this quantity was measured in four apparently healthy subjects once a month over 10 months. The coefficient of variation of the measurements was found to be between 2.7 and 4 per cent and in agreement with previously published data.

The effect of long-term dexfenfluramine treatment on 24-hour energy expenditure in man. A double-blind placebo controlled study.

In order to investigate the effect of long-term treatment with dexfenfluramine (dF) on 24-hour energy expenditure (EE), 10 obese females were studied in a double-blind design. Shortly before and 4 weeks after cessation of a 13 months treatment period with either dF (30 mg/day) or placebo (PL) the 24-hour EE was measured. The measurements were performed using a 24 m3 direct heat sink calorimeter with continuous real time measurements of evaporative and sensible heat losses. The patients performed a standardized program of exercise, rest and meals. The measurements were performed at 24 degrees C and at a humidity between 3 and 11 g/m3. Discontinuation of dF treatment did not change energy expenditure significantly from placebo, neither when expressed in kJ/kg lean body mass nor in kJ/kg body weight. After cessation of treatment total 24-hour EE decreased likewise nonsignificantly by 2.9 percent in the dF group and by 4.0 percent in the PL group. EE measured over 24 hours was subdivided into day and night periods and into resting energy expenditure as well as a measurement of the heat losses over a period of 3 hours after a meal. This subdivision of the EE showed similar nonsignificant differences. The conclusion is therefore that dF possesses no significant thermogenic effect during long-term administration in human obese subjects.

Negligible effects of previous moderate physical activity and changes in environmental temperature on whole body electrical impedance.

Several studies have shown that the predictive power of various linear combinations of anthropometric data (body weight, height, sex, age, etc.) to estimate fat free mass is improved after inclusion of measurements of electrical impedance (see eg Khaled et al., 1988). Published algorithms are based on measurements performed under fairly standardized conditions with the subjects at stationary conditions of rest, of environmental temperature and of body fluids. Use of the method under less standardized conditions raises the question of possible effects of deviations from these standard conditions. Hydration and dehydration by 1-2 l of fluid increased or decreased, respectively, the electrical resistance by about 14 per cent and the effects persisted for more than 1 h (Khaled et al., 1988). A change in environmental temperature by 21 degrees C from 35 degrees C to 14 degrees C (with almost constant relative humidity) during 90 min caused an increase in the resistance of about 9 per cent (Caton et al., 1988). The perturbations used in the studies quoted above are fairly drastic and not likely to occur under reasonably controlled field conditions. Therefore, we report here results of measurements of whole body electrical impedance before, during and after a period of 10 degrees C increased environmental temperature and before and after a 5-min period of light to moderate physical exercise.

The effect of a soluble dietary fibre supplement on 24-hour energy expenditure during a standardized physical activity programme.

Twenty-four hour energy expenditure during a standard physical activity programme was investigated in 19 healthy volunteers in a randomized, double-blind, cross-over design, after supplementation with a soluble dietary fibre amounting 7 g/day for 2 weeks. Energy intake and food fibre intake were kept constant during the treatment period. Twenty-four hour energy expenditure decreased insignificantly during fibre treatment (1.3 +/- 1.7 per cent). The dietary fibre supplement also had no significant effect on body weight, faecal energy loss or heart rate. Systolic blood pressure was insignificantly reduced during both placebo and fibre treatment (P = 0.09). There was, however, no difference between the groups after treatment.

Comparison of estimates of fat-free mass in normal and obese women from measurements of body potassium, body water and body density.

The relation between the estimates of fat-free mass (FFM) obtained from measurements of density, total body potassium and water was investigated in 104 women with Quetelet's Index between 19.9 and 49.7 kg/m2, body weight between 42.3 and 133.5 kg. The mean difference between the estimates based on water and potassium, previously reported as 2.2 kg or 4.4 per cent, was found to be independent of Quetelet's Index. The mean difference (s.e.m.) between the estimates of FFM based on density, compared with the average values from water and potassium, was found to be +7.0 (1.0), +6.3 (0.7) and +7.4 (1.1) kg in the ranges of Quetelet's Index 19.9-30.0, 30.1-40.0, and 40.1-49.7, respectively. The relative independence on Quetelet's Index of the difference between the estimates based on density compared with (water + potassium) is consistent with the idea that tissues of a higher density (ie, skin and bone) make up a larger proportion of the fat-free body weight in thin subjects than in fat ones.

Changes in energy expenditure of light physical activity during a 10 day period at 34 degrees C environmental temperature.

The energy expenditure of a 2 h programme of light activity was observed daily in 8 young men after a change in habitual environmental indoor temperature of 20-24 degrees C to 34 degrees C and an absolute humidity of 6-10 g/m3 during a 10 day period. No changes were observed with respect to the daily energy intake, body weight, rectal temperature and average skin temperature, but the energy expenditure showed a decrease of between 3 and 8 per cent. The observations support results of previous studies on acclimatization with respect to energy expenditure, and indicate that differences in energy expenditure due to habitual differences in environmental temperature are small, presumably less than 5 per cent.

Effect of 12 weeks' light-moderate underfeeding on 24-hour energy expenditure in normal male and female subjects.

The effect of 12 weeks' light-moderate underfeeding on the 24-h energy expenditure of a fixed physical activity programme was studied in six male and six female subjects. During a control period of 2 weeks, measurements were made of 24-h energy expenditure by direct calorimetry, the lean and fat body masses and the subjects' habitual energy intakes. The average body weight was 107 per cent of ideal, and did not change significantly during the control period. The subjects were asked to continue to record their daily food intake while reducing it by 25 per cent and to continue their daily activity habits during a period of 12 weeks. The mean change in body weight was -2.9 kg with an average change in body energy content of -66 MJ. The 24-h energy expenditure was measured three times during the period, ie, after 4, 8 and 12 weeks from the start of the decreased energy intake, and found to be practically the same as the control value, ie, with average differences (s.d.) of -0.2(3.9), -0.8(5.7) and +0.6(4.2) per cent from the control value. In the six subjects who had the largest loss of body weight, this was found to be 5.0 kg, and the mean differences (s.d.) in energy expenditure were found to be -1.0(3.4), 0.0(5.6) and -0.6(3.9) per cent, respectively, from the control value. A significant part of the between-subjects variation in the differences from the control value is due to random measurement error and it is concluded that a loss of body energy content of the magnitude reported here, and due mainly to a reduced food intake, does not result in a significant increase in the efficiency of energy conversion, ie, in metabolic adaptation.

Relation between energy expenditure and body composition in man: specific energy expenditure in vivo of fat and fat-free tissue.

The relationship between energy expenditure and body composition, in terms of fat and fat-free masses, has previously been described by a variety of predictive regression equations with parameters devoid of physiological content. We present here results obtained by calculating the specific energy expenditure, ie, the energy expenditure per unit of mass, of fat and fat-free tissue on the basis of measurements of the total energy expenditure (EE), the masses of fat (FM), and fat-free (FFM) tissue using the following simple model: EE = k1.FM + k2.FFM where k1 and k2 are the specific energy expenditures of fat and fat-free tissue, respectively. The results of observations on 104 women at rest yielded values for k1 and k2 of 0.31 and 1.35 watts/kg of fat and fat-free mass, respectively, with standard errors of estimate of 0.074 and 0.052 watts/kg, respectively. Analysis of several series of measurements, from other sources and on smaller samples of subjects, yielded similar values at rest but with larger standard errors of estimate. Data from subjects performing varying amounts of work in 24-h measurements showed, as expected, larger values for both tissues. The results explain to a very large extent the well-established relation between resting metabolic rate and body weight, ie, a linear relation with a non-zero intercept. The results also offer a clear-cut explanation for the well known difference in energy expenditure between men and women with the same body weight.

Energy expenditure during sleep in men and women: evaporative and sensible heat losses.

Evaporative and sensible heat losses were measured during sleep in 38 male and 21 female subjects in a direct whole-body calorimeter (24 m3). The subjects were all apparently healthy, had a mean body weight of 66 kg and had spent the preceding day in the calorimeter performing different fixed physical activity programmes. Heat losses were measured continuously between 11.30 p.m. and 6.30 a.m. The average (+/- s.e.m.) rate of total heat loss during the 7h of sleep was 90.6 +/- 1.21 and 74.4 +/- 1.22 watts for men and women respectively. The total heat loss during basal resting conditions immediately following sleep was 83.8 +/- 1.5 and 69.2 +/- 1.6 watts, respectively. Heat production during basal resting conditions, as measured by indirect calorimetry about 1 h after awakening on the morning of the preceding day, was found to be 85.6 +/- 1.3 and 71.2 +/- 1.1 watts, respectively. The increase in heat loss during sleep above that of basal resting conditions could largely be attributed to an increase in the evaporative heat loss. The heat loss fell during the night by about 14 per cent in women and about 30 per cent in men, approaching basal resting values in the last hour of sleep. Heat production during sleep was calculated for the male subjects by correcting the heat loss data for the published decreases in rectal temperature during the night and was found to be on average 9 per cent lower than the heat loss. The present data, as well as previously reported data, suggest that the energy expenditure of sleep is 0.95 X BMR rather than 1.0 X BMR as reported in the recent FAO/WHO/UNU Expert consultation (1985).

Effect of the preceding day's energy intake on the energy costs of rest, arm and leg exercise.

Relatively little is known about the response of the human body to perturbations in the energy intake. In particular, results of the effect of a perturbation of the preceding day's energy intake on the energy expenditure on the following day are conflicting, ranging from no effect at all to an increase in the resting metabolic rate of 12 per cent following an increase in the preceding day's energy intake of 5 MJ. In the present study, the fasting energy expenditure of rest, light arm work and light leg work was determined on days following an intake of 4, 10 and 16 MJ in seven healthy men. In each subject, the difference in energy expenditure between days following intakes on the preceding day of 10-10 (control), 10-4 and 10-16 MJ was calculated for each of the three tasks. The mean percentage differences between the days following an intake of 10-10, 10-4 and 10-16 MJ were (s.d. in parenthesis) 0.0 (4.0), +1.3 (4.0) and +0.6 (3.2) for the resting metabolic rate, -1.7 (4.0), -2.2 (3.2) and -1.7 (3.7) for arm work and +0.3 (2.0), -1.2 (2.9) and -0.3 (3.2) for leg work. When the differences for the three tasks were averaged, the results were -0.5 (1.4), -0.7 (2.4) and -0.5 (1.3) for the three combinations respectively. None of these differences were found to be statistically different from zero. Changes in plasma adrenaline and noradrenaline concentrations were also measured but found not to be related to the changes in energy expenditure or to the energy intakes.(ABSTRACT TRUNCATED AT 250 WORDS)