Energy metabolism after 2 y of energy restriction: the Biosphere 2 experiment

It has been hypothesized that the increased risk of obesity among African Americans may be partially explained by low energy expenditure (EE) and impaired fat oxidation. Twelve White adults without obesity were pair-matched by age, sex and body mass index (BMI) to a sample of 12 African Americans. Resting EE (REE), 24-h EE, 24-h RQ, Sleep EE, Sleep RQ and spontaneous physical activity were measured in a respiratory chamber; and free-living total daily EE (TDEE) and physical activity EE were measured using doubly labeled water. There were no race differences in age, body composition, 24-h RQ, sleep RQ, or spontaneous or free-living physical activity; however, Whites had significantly higher REE (p=0.02), 24-h EE (p=0.02), Sleep EE (p=0.005); but not TDEE (p=0.30) compared to African Americans after adjustment for FFM. African Americans may have a higher risk for obesity because of lower energy expenditure.

Weight loss is common among patients with Huntington's disease (HD), although the mechanisms contributing to this phenomenon are not known. We measured 24-hour sedentary energy expenditure (24-hour EE) and sleeping metabolic rate (SMR) in a human respiratory chamber in 17 patients with mild to moderate HD and 17 control subjects matched for age, sex, and body mass index. Total energy expenditure was measured during 7 days in free-living conditions, using the doubly labeled water technique. Body weight, fat mass, and fat-free mass (measured by dual-energy x-ray absorptiometry) were similar in patients with HD and control subjects. Twenty-four-hour EE was 14% higher in HD patients than controls in absolute terms (2,038+/-98 vs 1,784+/-68 kcal/24 hours) and after adjustment for age, sex, fat mass, and fat-free mass (1,998+/-45 vs. 1,824+/-45 kcal/24 hours). In contrast, SMR and total energy expenditure were similar in patients and controls both in absolute terms (1,314+/-38 vs 1,316+/-42 and 2,402+/-102 vs. 2,373+/-98 kcal/24 hours, respectively) and after adjustment. Spontaneous physical activity measured by radar in the chamber and the ratio of 24-hour EE to SMR were significantly higher in HD patients than controls (11.4+/-1.4 vs 6.1+/-0.6% and 1.54+/-0.05 vs 1.36+/-0.03, respectively). In the group as a whole, 24-hour EE/SMR correlated with spontaneous physical activity. Among HD patients, both 24-hour EE/SMR and spontaneous physical activity correlated with the severity of chorea, but SMR and total energy expenditure did not. There were no differences in reported energy intake during 7 days in patients with HD compared with controls. The results of this study indicate that sedentary energy expenditure is higher in patients with HD than in controls in proportion to the severity of the movement disorder. Total free-living energy expenditure is not higher, however, because patients with HD appear to engage in less voluntary physical activity.

Weight loss is common among patients with Huntington's disease (HD), although the mechanisms contributing to this phenomenon are not known. We measured 24-hour sedentary energy expenditure (24-hour EE) and sleeping metabolic rate (SMR) in a human respiratory chamber in 17 patients with mild to moderate HD and 17 control subjects matched for age, sex, and body mass index. Total energy expenditure was measured during 7 days in free-living conditions, using the doubly labeled water technique. Body weight, fat mass, and fat-free mass (measured by dual-energy x-ray absorptiometry) were similar in patients with HD and control subjects. Twenty-four-hour EE was 14% higher in HD patients than controls in absolute terms (2,038 ± 98 vs 1,784 ± 68 kcal/24 hours) and after adjustment for age, sex, fat mass, and fat-free mass (1,998 ± 45 vs 1,824 ± 45 kcal/24 hours). In contrast, SMR and total energy expenditure were similar in patients and controls both in absolute terms (1,314 ± 38 vs 1,316 ± 42 and 2,402 ± 102 vs 2,373 ± 98 kcal/24 hours, respectively) and after adjustment. Spontaneous physical activity measured by radar in the chamber and the ratio of 24-hour EE to SMR were significantly higher in HD patients than controls (11.4 ± 1.4 vs 6.1 ± 0.6% and 1.54 ± 0.05 vs 1.36 ± 0.03, respectively). In the group as a whole, 24-hour EE/SMR correlated with spontaneous physical activity. Among HD patients, both 24-hour EE/SMR and spontaneous physical activity correlated with the severity of chorea, but SMR and total energy expenditure did not. There were no differences in reported energy intake during 7 days in patients with HD compared with controls. The results of this study indicate that sedentary energy expenditure is higher in patients with HD than in controls in proportion to the severity of the movement disorder. Total free-living energy expenditure is not higher, however, because patients with HD appear to engage in less voluntary physical activity. Ann Neurol 2000; 47:64–70

Physical Activity and the Missing Calories.

Identifying whether components of total energy expenditure (EE) are affected by orexin receptor (OXR1 and OXR2) stimulation or antagonism with dual orexin receptor antagonists (DORAs) has relevance for obesity treatment. Orexin receptor stimulation reduces weight gain by increasing total EE and EE during spontaneous physical activity (SPA). The purpose of this study was to determine if a DORA (TCS-1102) in the ventrolateral preoptic area (VLPO) reduced orexin-A-induced arousal, SPA, total EE and EE during sleep, rest, wake and SPA and whether the DORA alone reduced total EE and its components. We hypothesized that: (1) a DORA would reduce orexin-A induced increases in arousal, SPA, components of total EE, reductions in sleep and the EE during sleep and (2) the DORA alone would reduce baseline (non-stimulated) SPA and total EE. Sleep, wakefulness, SPA and EE were determined after microinjection of the DORA (TCS-1102) and orexin-A in the VLPO of male Sprague-Dawley rats with a unilateral cannula targeted towards the VLPO. Individual components of total EE were determined based on time-stamped data. The DORA reduced orexin-A-induced increases in arousal, SPA, total EE and EE during SPA, wake, rest and sleep 1 h post injection (P<0.05). Orexin-A significantly reduced sleep and significantly increased EE during sleep 1 h post injection (P<0.05). Furthermore, the DORA alone significantly reduced total EE, EE during sleep (NREM and REM) and resting EE 2 h post injection (P<0.05). These data suggest that orexin-A reduces weight gain by stimulating total EE through increases in EE during SPA, rest and sleep. Residual effects of the DORA alone include decreases in total EE and EE during sleep and rest, which may promote weight gain.

To assess the impact of Type 2 (non-insulin-dependent) diabetes mellitus on energy metabolism, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were measured in a respiratory chamber in 151 Pima Indians, 102 with normal glucose tolerance (67 male/35 female, (mean +/- SD) 28 +/- 7 years, 99 +/- 24 kg, 32 +/- 9% body fat) and in 49 with Type 2 diabetes (22 male/27 female, 35 +/- 11 years, 107 +/- 33 kg, 39 +/- 7% body fat), after at least 3 days on a weight maintaining diet. After adjustment for differences in fat-free mass, fat mass, age and sex, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were significantly higher in diabetic patients than in control subjects (72 kcal/day, p less than 0.05; 99 kcal/day, p less than 0.005; 99 kcal/day, p less than 0.001 respectively). Spontaneous physical activity was similar in both groups whereas the thermic effect of food, calculated as the mean energy expenditure corrected for activity throughout the day above sleeping metabolic rate and expressed as a percentage of energy intake, was significantly lower in Type 2 diabetic patients (17.1 +/- 7.1 vs 19.8 +/- 5.6%, p less than 0.05). Adjusted values of 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were correlated with hepatic endogenous glucose production (r = 0.22, p less than 0.05; r = 0.22, p less than 0.05; r = 0.31, p less than 0.01 respectively). Therefore, increased basal and sleeping metabolic rates, resulting in increased 24-h sedentary energy expenditure may play a role in the weight loss so often observed in Type 2 diabetic subjects in addition to the energy loss from glycosuria.

The aim of this study was to determine whether overweight and obese individuals with type 2 diabetes have higher basal and 24-h energy expenditure compared with healthy control subjects before and after adjustment for body composition, spontaneous physical activity (SPA), sex, and age. Data from 31 subjects with type 2 diabetes and 61 nondiabetic control subjects were analyzed. The 24-h energy expenditure, basal metabolic rate (BMR), and sleeping energy expenditure (EEsleep) between 1:00 a.m. and 6:00 a.m. were measured in whole-body respiratory chambers. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). No significant differences in unadjusted EEsleep, BMR, and 24-h energy expenditure were observed between the type 2 diabetic group and the control group. After adjustment for fat-free mass (FFM), fat mass, SPA, sex, and age, EEsleep and BMR were, respectively, 7.7 and 6.9% higher in the type 2 diabetic group compared with the control group. This was equivalent to 144 +/- 40 kcal/day (P = 0.001) and 139 +/- 61 kcal/day (P = 0.026), respectively. Adjusted 24-h energy expenditure was 6.5% higher in the type 2 diabetic group compared with the nondiabetic control subjects (2,679 +/- 37 vs. 2,515 +/- 23 kcal/day, P = 0.002). In multiple regression analyses, FFM, fat mass, SPA, and diabetes status were all significant determinants of EEsleep and 24-h energy expenditure, explaining 83 and 81% of the variation, respectively. This study confirms reports in Pima Indians that basal and 24-h energy expenditure adjusted for body composition, SPA, sex, and age are higher in individuals with type 2 diabetes compared with nondiabetic control subjects and may be even more pronounced in Caucasians.

To examine the causes of weight gain occurring as an adverse effect of treatment of hyperthyroidism. We measured 24-h energy expenditure (EE), body composition and spontaneous physical activity (SPA) in eight patients before and 1 year after treatment of hyperthyroidism was initiated, and eight controls. One year after initiation of treatment thyrotropin was normalized, thyroid hormones had fallen to the lower end of the reference range and fat mass had increased by 3.5 kg (p < 0.001). Twenty-four hour EE adjusted for fat-free mass (FFM) was 15% higher in hyperthyroid patients before treatment than in controls (p = 0.003), and treatment decreased 24-h EE by 1.9 MJ/day (p = 0.001). After treatment, 24-h EE, adjusted for FFM, was similar to the controls. Multiple regression analyses showed that the suppressed EE could partly be attributed to an iatrogenic suppression of thyroid hormones, resulting in lower sleeping EE. Twenty-four hour SPA was normal in the hyperthyroid state, but decreased after treatment by 21% (p = 0.045), to a level not significantly different, but still below that of the controls. The study suggests that weight gain during treatment of hyperthyroidism might be due to subnormal levels of EE and SPA caused by a suppression of the thyroid hormone to a level in the lower end of the normal range.

To discuss the potential importance of spontaneous physical activity in regulating body weight and outline possible reasons for the large interindividual variance in spontaneous physical activity. Spontaneous physical activity is highly variable among people, with some having high levels and some low, and can contribute significantly to interindividual differences in total daily energy expenditure. Cross-sectionally, spontaneous physical activity is inversely related to body weight; however, more importantly, spontaneous physical activity is inversely associated with weight gain in prospective studies, and experimental weight perturbations do not appear to change spontaneous physical activity behavior. Spontaneous physical activity is a familial trait and is biologically influenced, although the environment exerts a significant impact. Although spontaneous physical activity is a biologically driven behavior, interventions to increase nonexercise activity within the workplace and school hold promise in increasing daily energy expenditure for the average sedentary American. However, many large-scale efforts will need to take place within our sedentary-promoting environment to encourage more daily spontaneous physical activity-related activity.

The gene that codes for a novel uncoupling protein, UCP2, has been linked to obesity in animal models. Markers encompassing the UCP2 locus have been linked to energy expenditure in humans. We studied the role of a common amino acid substitution, replacing an alanine (A) with a valine (V) at codon 55, of the coding region of the UCP2 gene for 24-h energy expenditure and respiratory quotient (RQ) in healthy subjects 24-h energy expenditure and RQ were measured in calorimeters in 60 healthy subjects. The UCP2 polymorphism was determined by restriction fragment length polymorphism-generating polymerase chain reaction. Age, gender and body fat were not different between groups, the number of subjects in each groups was A/A: 35% (n=21), A/V: 48% (n=29), and V/V: 17% (n=10). Twenty-four-hour energy expenditure, adjusted for fat-free mass, fat mass, and spontaneous physical activity, was 311 kJ/d lower (95% confidence interval: 24-598 kJ/d, P=0.03) in the V/V homozygotes than in the A/A and A/V genotypes. The V/V had approximately 20% higher 24-h spontaneous physical activity, particularly higher at night (P<0.005). Energy expenditure due to higher spontaneous physical activity counteracted the V/V group's lower 24-h resting energy expenditure for a given body size and composition. 24-h RQ adjusted for energy balance, age, sex and spontaneous physical activity, was higher in the V/V homozygotes than in the AA and A /V groups (P<0.05). Subjects with the V/V genotype of the UCP2 gene exhibit an enhanced metabolic efficiency and lower fat oxidation than the A/A and A/V genotypes.

Assessment of total energy expenditure in free-living patients with cystic fibrosis

Age and sex effects on energy expenditure

The present study assessed the possible familial effect in 71 healthy Caucasian siblings on each of the variables determining the inter-individual variations in energy expenditure (EE) measured under standardized conditions. We found that the 24-h EE measured in respiration chambers of 71 siblings from 32 different families was positively correlated with fat-free mass, which explained 82% of the variation between subjects (P < 0.00001). An additional 10% of the total variation was explained by differences in spontaneous physical activity (P < 0.00001), fat mass (P < 0.00001), plasma concentration of free T3 (P < 0.003), and norepinephrine (P < 0.002), whereas plasma values of epinephrine and androgen hormones did not correlate with 24-h EE. After adjustment for gender, there was a familial aggregation of both 24-h and sleeping EE, as indicated by intraclass correlation coefficients (r) of 0.44 (P < 0.02) and 0.58 (P < 0.01), respectively. The familial effect on gender-adjusted 24-h EE was explained mainly by a familial resemblance of fat-free mass (ri = 0.48; P < 0.015) and fat mass (ri = 0.40; P < 0.03), whereas spontaneous physical activity and plasma concentrations of T2 and norepinephrine did not correlate in families. It is concluded that the familial aggregation of EE in Caucasians is mediated mainly through familial resemblance of body composition; even though plasma concentrations of free T3 and norepinephrine, independent of body composition, explain an additional proportion of the variation in EE, they do not contribute to the familial correlation.

Energy expenditure in narcolepsy patients and controls

Obesity treatments aim to maximize fat loss, particularly abdominal or visceral fat, without compromising lean or bone mass. However, the literature contains numerous examples of obesity treatments that - in addition to fat loss - result in loss of lean mass and/or bone mass. Because of the known effects of energy restriction to increase activity of the hypothalamo-pitutiary adrenal (HPA) axis in lean humans and animals, and because increases in circulating glucocorticoid levels could potentially contribute to adverse body compositional changes with obesity treatments, we conducted a systematic PubMed search to determine whether HPA axis activation also occurs in response to energy restriction in obese humans and animals. In most studies in obese humans, short-term severe energy restriction increased circulating cortisol levels, and this response was also seen in two longer-term human studies involving severe or moderate energy restriction. These findings parallel studies on short- or long-term energy restriction in obese rodents, with most studies showing increases in circulating corticosterone concentrations, and no change or actual increases in hypothalamic expression of corticotropin-releasing hormone, urocortin 3 or their receptors. However, a significant proportion of studies involving longer-term severe or moderate energy restriction in obese humans showed no change or decreases in HPA axis function. There was variability among human studies in the duration of energy restriction and timing of the HPA axis investigations (i.e., during energy restriction, or after a period of post-restriction weight maintenance). In order to unambiguously determine changes in HPA axis function with energy restriction in obese humans, it will be important to assess HPA axis function at multiple time points during energy restriction, given that obese individuals may spend many weeks or months in severe or moderate energy restriction in order to reduce excess weight, and given that increases in glucocorticoid function can have significant effects on body composition within weeks to months.