Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure.

Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.

Variability in energy expenditure is much greater in males than females.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition.

Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested.

Physical activity and fat-free mass during growth and in later life.

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass. OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age. METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution. RESULTS: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively. CONCLUSIONS: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.

Energy compensation and adiposity in humans.

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

A standard calculation methodology for human doubly labeled water studies.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

BACKGROUND: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition. The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). METHODS: 148 subjects (39 men, 109 women), mean ±â€¯SD age: 41 ±â€¯9 year; body mass index (BMI): 31.9 ±â€¯3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters. RESULTS: The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss. CONCLUSION: Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.

Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

BACKGROUND: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). METHODS: 148 subjects (39 men, 109 women), mean ±â€¯SD age: 41 ±â€¯9 year; body mass index (BMI): 31.9 ±â€¯3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters. RESULTS: The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss. CONCLUSION: Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.

Physical activity and weight loss are independent predictors of improved insulin sensitivity following energy restriction.

OBJECTIVE: The role of physical activity and the joint effect with sleep duration on insulin sensitivity (IS) during energy restriction followed by weight maintenance were determined. METHODS: One hundred and two subjects (28 males) (mean ± SD age: 40 ± 9 years; BMI: 31.9 ± 3.0 kg/m(2) ) followed a very-low-energy diet for 8 weeks, followed by a 44-week period of weight maintenance. Body composition (three-compartment model based on body weight, total body water, and body volume), physical activity (accelerometry), sleep (questionnaire, Epworth Sleepiness Scale), and fasting plasma insulin and glucose concentrations were assessed before the diet and at 8, 20, and 52 weeks after the start. RESULTS: Compared to baseline, IS was improved significantly after 8 weeks (P < 0.001) and was higher after 20 weeks (P < 0.001) and 52 weeks (P < 0.05). After 8, 20, and 52 weeks, 23% (P < 0.01), 19% (P < 0.05), and 13% (P < 0.05), respectively, of the variance in IS improvement was explained by weight loss percentage and change in physical activity counts. CONCLUSIONS: Maintaining daily physical activity during energy restriction is as important as weight loss itself in the improvement of IS; there was no additional effect of change in sleep duration. During weight maintenance, improved IS is maintained better if physical activity returns to baseline or higher.

Weight loss-induced changes in adipose tissue proteins associated with fatty acid and glucose metabolism correlate with adaptations in energy expenditure.

BACKGROUND: Energy restriction causes adaptations in energy expenditure (total-,TEE; resting-,REE; activity induced-,AEE). OBJECTIVE: To determine if changes in the levels of proteins involved in adipocyte glucose and fatty acid metabolism as indicators for energy deficiency are related to adaptations in energy expenditure during weight loss. METHODS: Forty-eight healthy subjects (18 men, 30 women), mean ± SD age 42 ± 8 y and BMI 31.4 ± 2.8 kg/m(2), followed a very low energy diet for 8 wk. Protein levels of fatty acid binding protein 4 (FABP4), fructose-bisphosphate aldolase C (AldoC) and short chain 3-hydroxyacyl-CoA dehydrogenase (HADHsc) (adipose tissue biopsy, western blot), TEE (doubly labeled water), REE (ventilated hood), and AEE were assessed before and after the 8-wk diet. RESULTS: There was a positive correlation between the decrease in AldoC and the decrease in TEE (R = 0.438, P < 0.01) and the decrease change in AEE (R = 0.439, P < 0.01). Furthermore, there was a negative correlation between the increases in HADHsc and the decrease in REE (R = 0.343, P < 0.05). CONCLUSION: The decrease in AldoC correlated with the decrease in AEE, which may be explained by a decreased glycolytic flux. Additionally, the change in HADHsc, a crucial enzyme for a step in beta-oxidation, correlated with the adaptation in REE. CLINICAL TRIAL REGISTRATION NUMBER: NCT01015508 at clinicaltrials.gov.

Leptin and energy restriction induced adaptation in energy expenditure.

BACKGROUND: Diet-induced weight loss is accompanied by adaptive thermogenesis, i.e. a disproportional reduction of resting energy expenditure (REE) a decrease in physical activity and increased movement economy. OBJECTIVE: To determine if energy restriction induced adaptive thermogenesis and adaptations in physical activity are related to changes in leptin concentrations. METHODS: Eighty-two healthy subjects (23 men, 59 women), mean ± SD age 41 ± 8 years and BMI 31.9 ± 3.0 kg/m(2), followed a very low energy diet for 8 weeks with measurements before and after the diet. Leptin concentrations were determined from fasting blood plasma. Body composition was assessed with a three-compartment model based on body weight, total body water (deuterium dilution) and body volume (BodPod). REE was measured (REEm) with a ventilated hood and predicted (REEp) from measured body composition. Adaptive thermogenesis was calculated as REEm/REEp. Parameters for the amount of physical activity were total energy expenditure expressed as a multiple of REEm (PAL), activity-induced energy expenditure divided by body weight (AEE/kg) and activity counts measured by a tri-axial accelerometer. Movement economy was calculated as AEE/kg (MJ/kg/d) divided by activity counts (Mcounts/d). RESULTS: Subjects lost on average 10.7 ± 4.1% body weight (P<0.001). Leptin decreased from 26.9 ± 14.3 before to 13.9 ± 11.3 µg/l after the diet (P<0.001). REEm/REEp after the diet (0.963 ± 0.08) was related to changes in leptin levels (R(2)=0.06; P<0.05). There was no significant correlation between changes in leptin concentrations and changes in amount of physical activity. Movement economy changed from 0.036 ± 0.011 J/kg/count to 0.028 ± 0.010 J/kg/count and was correlated to the changes in leptin concentrations (R(2)=0.07; P<0.05). CONCLUSION: During energy restriction, the decrease in leptin explains part of the variation in adaptive thermogenesis. Changes in leptin are not related to the amount of physical activity but could partly explain the increased movement economy.

Genetic predisposition, dietary restraint and disinhibition in relation to short and long-term weight loss.

BACKGROUND: Interindividual differences in response to weight loss and maintenance thereafter are ascribed to genetic predisposition and behavioral changes. OBJECTIVE: To examine whether body weight and short and long-term body weight loss were affected by candidate single nucleotide polymorphisms (SNPs) and changes in eating behavior or by an interaction between these genetic and behavioral factors. METHODS: 150 healthy subjects (39 males, 111 females) aged 20-50 y with a BMI of 27-38 kg/m(2) followed a very low energy diet for 8-weeks, followed by a 3-month weight maintenance period. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG, PPARD, and PPARGC1A. Changes in eating behavior were determined with the Three Factor Eating Questionnaire. RESULTS: A high genetic predisposition score was associated with a high body weight at baseline and more short-term weight loss. From the six selected obesity-related SNPs, FTO was associated with increased body weight at baseline, and the effect allele of PPARGC1A was positively associated with short-term weight loss, when assessed for each SNP separately. Long-term weight loss was associated with a larger increase in dietary restraint and larger decrease in disinhibition. CONCLUSION: During long-term weight loss, genetic effects are dominated by changes in eating behavior.

Concomitant changes in sleep duration and body weight and body composition during weight loss and 3-mo weight maintenance.

BACKGROUND: An inverse relation between sleep duration and body mass index (BMI) has been shown. OBJECTIVE: We assessed the relation between changes in sleep duration and changes in body weight and body composition during weight loss. DESIGN: A total of 98 healthy subjects (25 men), aged 20-50 y and with BMI (in kg/m(2)) from 28 to 35, followed a 2-mo very-low-energy diet that was followed by a 10-mo period of weight maintenance. Body weight, body composition (measured by using deuterium dilution and air-displacement plethysmography), eating behavior (measured by using a 3-factor eating questionnaire), physical activity (measured by using the validated Baecke's questionnaire), and sleep (estimated by using a questionnaire with the Epworth Sleepiness Scale) were assessed before and immediately after weight loss and 3- and 10-mo follow-ups. RESULTS: The average weight loss was 10% after 2 mo of dieting and 9% and 6% after 3- and 10-mo follow-ups, respectively. Daytime sleepiness and time to fall asleep decreased during weight loss. Short (≤7 h) and average (>7 to <9 h) sleepers increased their sleep duration, whereas sleep duration in long sleepers (≥9 h) did not change significantly during weight loss. This change in sleep duration was concomitantly negatively correlated with the change in BMI during weight loss and after the 3-mo follow-up and with the change in fat mass after the 3-mo follow-up. CONCLUSIONS: Sleep duration benefits from weight loss or vice versa. Successful weight loss, loss of body fat, and 3-mo weight maintenance in short and average sleepers are underscored by an increase in sleep duration or vice versa. This trial was registered at clinicaltrials.gov as NCT01015508.

Physiological response of adipocytes to weight loss and maintenance.

BACKGROUND: Metabolic processes in adipose tissue are dysregulated in obese subjects and, in response to weight loss, either normalize or change in favor of weight regain. OBJECTIVE: To determine changes in adipocyte glucose and fatty acid metabolism in relation to changes in adipocyte size during weight loss and maintenance. METHODS: Twenty-eight healthy subjects (12 males), age 20-50 y, and BMI 28-35 kg/m(2), followed a very low energy diet for 2 months, followed by a 10-month period of weight maintenance. Body weight, body composition (deuterium dilution and BodPod), protein levels (Western blot) and adipocyte size were assessed prior to and after weight loss and after the 10-month follow-up. RESULTS: A 10% weight loss resulted in a 16% decrease in adipocyte size. A marker for glycolysis decreased (AldoC) during weight loss in association with adipocyte shrinking, and remained decreased during follow-up in association with weight maintenance. A marker for fatty acid transport increased (FABP4) during weight loss and remained increased during follow-up. Markers for mitochondrial beta-oxidation (HADHsc) and lipolysis (ATGL) were only increased after the 10-month follow-up. During weight loss HADHsc and ATGL were coordinately regulated, which became weaker during follow-up due to adipocyte size-related changes in HADHsc expression. AldoC was the major denominator of adipocyte size and body weight, whereas changes in ATGL during weight loss contributed to body weight during follow-up. Upregulation of ATGL and HADHsc occured in the absence of a negative energy balance and was triggered by adipocyte shrinkage or indicated preadipocyte differentiation. CONCLUSION: Markers for adipocyte glucose and fatty acid metabolism are changed in response to weight loss in line with normalization from a dysregulated obese status to an improved metabolic status. TRIAL REGISTRATION: ClinicalTrials.gov NCT01015508.

Weight loss, weight maintenance, and adaptive thermogenesis.

BACKGROUND: Diet-induced weight loss is accompanied by adaptive thermogenesis, ie, a disproportional or greater than expected reduction of resting metabolic rate (RMR). OBJECTIVE: The aim of this study was to investigate whether adaptive thermogenesis is sustained during weight maintenance after weight loss. DESIGN: Subjects were 22 men and 69 women [mean ± SD age: 40 ± 9 y; body mass index (BMI; in kg/m(2)): 31.9 ± 3.0]. They followed a very-low-energy diet for 8 wk, followed by a 44-wk period of weight maintenance. Body composition was assessed with a 3-compartment model based on body weight, total body water (deuterium dilution), and body volume. RMR was measured (RMRm) with a ventilated hood. In addition, RMR was predicted (RMRp) on the basis of the measured body composition: RMRp (MJ/d) = 0.024 × fat mass (kg) + 0.102 × fat-free mass (kg) + 0.85. Measurements took place before the diet and 8, 20, and 52 wk after the start of the diet. RESULTS: The ratio of RMRm to RMRp decreased from 1.004 ± 0.077 before the diet to 0.963 ± 0.073 after the diet (P < 0.001), and the decrease was sustained after 20 wk (0.983 ± 0.063; P < 0.01) and 52 wk (0.984 ± 0.068; P < 0.01). RMRm/RMRp was correlated with the weight loss after 8 wk (P < 0.01), 20 wk (P < 0.05), and 52 wk (P < 0.05). CONCLUSION: Weight loss results in adaptive thermogenesis, and there is no indication for a change in adaptive thermogenesis up to 1 y, when weight loss is maintained. This trial was registered at clinicaltrials.gov as NCT01015508.