Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

BACKGROUND: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. OBJECTIVE: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. METHODS: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold) or 24°C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. RESULTS: We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. CONCLUSIONS: It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.

An approach to quantifying abnormalities in energy expenditure and lean mass in metabolic disease.

BACKGROUND/OBJECTIVES: The objective of this study was to develop approaches to expressing resting energy expenditure (REE) and lean body mass (LM) phenotypes of metabolic disorders in terms of Z-scores relative to their predicted healthy values. SUBJECTS/METHODS: Body composition and REE were measured in 135 healthy participants. Prediction equations for LM and REE were obtained from linear regression and the range of normality by the standard deviation of residuals. Application is demonstrated in patients from three metabolic disorder groups (lipodystrophy, n=7; thyrotoxicosis, n=16; and resistance to thyroid hormone (RTH), n=46) in which altered REE and/or LM were characterised by departure from the predicted healthy values, expressed as a Z-score. RESULTS: REE (kJ/min) = -0.010 × age (years)+0.016 × FM (kg)+0.054 × fat-free mass (kg)+1.736 (R2 = 0.732, RSD = 0.36 kJ/min). LM (kg)=5.30 × bone mineral content (kg)+10.66 × height2 (m)+6.40 (male). LM (kg)=0.20 × fat (kg)+14.08 × height2 (m)-2.93 (female).(male R2=0.55, RSD = 3.90 kg; female R2 = 0.59, RSD=3.85 kg).We found average Z-scores for REE and LM of 1.77 kJ/min and -0.17 kg in the RTH group, 5.82 kJ/min and -1.23 kg in the thyrotoxic group and 2.97 kJ/min and 4.20 kg in the LD group. CONCLUSION: This approach enables comparison of data from individuals with metabolic disorders with those of healthy individuals, describing their departure from the healthy mean by a Z-score.

Prediction of weight loss and regain following dietary, lifestyle, and pharmacologic intervention.

To develop statistical models for predicting weight loss and regain, we analyzed the phenotypic responses in an outpatient study of 60 obese subjects randomized to one of three 12-week interventions, diet (-600 kcal) alone, diet with exercise, and diet with sibutramine. This was followed by 12 weeks of observation. The best of the "baseline covariates" models was one that incorporated intervention group and baseline homeostasis model assessment-estimated insulin resistance (HOMA(IR)). It predicted week 12 weight change with R(2) of 0.38 and root mean square error (√MSE) of 2.92 kg. An alternative model incorporating baseline fat mass plus change in weight and HOMA(IR) at week 4 improved the prediction (R(2), 0.67, √MSE, 2.19 kg). We could not identify a satisfactory model to predict weight regain. We conclude that prediction of weight loss over 12 weeks is significantly improved when short-term weight change is incorporated into the model. This information could be utilized to forecast the success of a weight-loss program and to motivate and contribute to innovative designing of obesity trials.

Insulin sensitivity and body composition in children with classical and nonclassical congenital adrenal hyperplasia.

BACKGROUND: Reduced insulin sensitivity and increased fat mass have been reported in children and adults with congenital adrenal hyperplasia (CAH). To understand the potential mechanisms underlying these differences, we assessed insulin sensitivity and body composition in children with classical or nonclassical (late-presenting) CAH compared with normal controls. SUBJECTS AND METHODS: Thirty-seven children with CAH (26 classical and 11 nonclassical) median (range) age 9.4 year (0.5-15.8) were compared with 41 healthy control children age 11.0 year (3.2-17.1). All children had an overnight fasting blood sample and body composition assessed by DEXA. Pubertal children (14 CAH and 19 controls) also had an oral glucose tolerance test. Classical and nonclassical CAH groups were each compared with controls, adjusting for age, gender and pubertal status. Results Classical CAH children had more fat mass than controls (P = 0.03), while nonclassical CAH children had more lean mass (P = 0.006) and higher systolic blood pressure (P = 0.003) than control children. Among pubertal children, nonclassical CAH children had higher mean insulin (0-120 min; P = 0.04), stimulated insulin (0-30 min; P = 0.02), 120 min insulin (P = 0.004) and 120 min glucose levels (P = 0.03) than controls, but no difference in disposition index. DISCUSSION: Greater body fat in classical (early-presenting) CAH children could reflect the effects of lifetime glucocorticoid therapy. In contrast, the greater lean mass and parameters of insulin resistance in nonclassical (late-presenting) CAH children likely indicate the adverse metabolic effects of prolonged postnatal androgen excess.

Validity of the leg-to-leg bioimpedance to estimate changes in body fat during weight loss and regain in overweight women: a comparison with multi-compartment models.

OBJECTIVES: To investigate changes in body composition and the validity of the leg-to-leg bioimpedance (LTL) method to measure body fat during active weight loss (WL) and weight regain (WR). DESIGN: Longitudinal, 12-week weight loss intervention (3.3-3.8 MJ/day) and subsequent follow-up at 1 year. SUBJECTS: Fifty-eight adult women aged between 24 and 65 years (mean age: 46.8+/-8.9 years) and with a body mass index (BMI) > or =25 kg/m(2) (mean BMI: 31.6+/-2.5 kg/m(2), range=26.0-48.2 kg/m(2)) participated in the study. MEASUREMENTS: Fat mass (FM) was measured at baseline, 12 weeks, 24 weeks and 52 weeks using three- and four-compartment (4-C) models, air displacement plethysmography (ADP), deuterium dilution - total body water (TBW), dual-energy X-ray absorptiometry (DXA), skinfold thickness (SFT), tetrapolar bioelectrical impedance analysis (T-BIA) and LTL. RESULTS: At the end of the weight loss programme, subjects lost 9.9+/-3.5 kg weight (P<0.001) and 7.6+/-0.5 kg fat (P<0.001) but after 1 year they had regained 4.9+/-3.7 kg of weight and 3.7+/-2.9 kg of fat. The 4-C model showed that FM and TBW accounted for 76.2 and 23.6% of the loss in body mass and 81.8 and 17.7% of the tissue accrued during weight regain, respectively. The estimate of body fat change by LTL relative to multi-compartment models (WL(bias+/-2s.d.)=0.51+/-3.26 kg; WR(bias+/-2s.d.)=-0.25+/-2.30 kg) was similar to ADP, DXA and TBW in both phases but it was better than T-BIA (WL(bias+/-2s.d.)=0.17+/-7.90 kg; WR(bias+/-2s.d.)=-0.29+/-7.59 kg) and skinfold thickness (WL(bias+/-2s.d.)=2.68+/-6.68 kg; WR(bias+/-2s.d.)=-0.84+/-3.80 kg). CONCLUSIONS: Weight loss and regain were associated with minimal changes in lean tissue as measured using multi-compartment models. The LTL system is a useful method to measure body composition changes during clinical weight management programmes.

Variability of appetite control mechanisms in response to 9 weeks of progressive overfeeding in humans.

BACKGROUND: The current epidemic of obesity demonstrates that mechanisms for maintaining human energy balance are readily subverted by adverse environmental conditions. The critical elements of this dysregulation are poorly understood. Most previous research into what regulates the intake side of the energy balance equation has been handicapped by the use of short-term within-day experimental tests. OBJECTIVE: We enrolled six non-obese men to a 17-week protocol involving three 21 days periods of progressive overfeeding (+20, +40 and +60%) separated by free diet periods to test for compensatory satiety. RESULTS: Responses to overfeeding differed markedly with evidence of 'compensators' and 'non-compensators', but on average, subsequent food intake was stimulated rather than suppressed after overfeeding in spite of markedly elevated body fat (+13%) and fasting leptin (+116%). DISCUSSION: The inefficient response of in-built appetite control mechanisms emphasizes the need to adopt intentional cognitive restraint in the modern environment when food is plentiful.

Leptin does not respond to 48 h fat deposition or mobilization in women.

OBJECTIVE: To test the hypothesis that acute responses of plasma leptin concentration to energy balance manipulation are mediated by fat flux. DESIGN: Ten healthy women aged 31-63 y, mass 48-113.5 kg, fat mass 8.5-62.5 kg, were studied for 3 days in a whole-body calorimeter on two occasions. After a control day (D1) during which energy balance was maintained, diet was manipulated to induce fat deposition (FD) or mobilization (FM) of 50 g/day for 2 days (D2 & D3). A difference totalling of 194+/-18.6 g fat was achieved between manipulations without significant effects on carbohydrate or protein balance. Fasting plasma leptin was measured on D2 and D4. RESULTS: After the control day plasma leptin concentration averaged 19.01+/-9.8 ng/ml, and was found to be linearly related to body fat mass. After 2 days manipulation of fat balance, leptin concentrations were 21.4+/-10.3 ng/ml (FD) and 21.2+/-11.3 ng/ml (FM). There was no significant difference between treatments in either control day or postmanipulation leptin concentrations, nor did the treatments induce any differences in glucose or insulin concentration responses. CONCLUSION: Although in states of energy balance leptin concentration is linearly related to fat mass, acute modulation of leptin concentration during energy imbalance is not mediated by fat flux.

Dose-response relationship between fat ingestion and oxidation: quantitative estimation using whole-body calorimetry and 13C isotope ratio mass spectrometry.

OBJECTIVE: To determine dose-dependent relationship between ingested fat and its oxidation in the immediate post-prandial period in humans. DESIGN: Subjects were randomly selected for the study at the Dunn Clinical Nutrition Centre, Cambridge, UK. Subjects ingested naturally enriched 13C corn-oil doses (range 20-140g) in a whole-body indirect calorimeter, and were studied for 8 h. Ingested fat oxidation was estimated from the subject's breath 13C enrichment and total carbon dioxide production. Total fat and carbohydrate oxidation were estimated from non-protein oxygen and carbon dioxide exchanges. Endogenous fat oxidation was estimated as the difference between total fat and ingested fat oxidation. RESULTS: The amount of fat dose oxidized was nonlinearly related to the amount ingested. On average, 25.6+/-2.7% of the mean fat dose was oxidized. A significant (r = - 0.72, P < 0.001) inverse correlation was found between the amount of fat dose and the proportion oxidized. Endogenous carbohydrate oxidation was negatively and significantly correlated to fat dose oxidized (r= -0.61, P < 0.01), but it was not correlated to endogenous fat oxidation. CONCLUSIONS: There was a nonlinear relationship between amount of fat dose and its quantity that was oxidized in the immediate post-prandial period. The inverse relationship between the size of the fat load and the proportion that was oxidized post-prandially implies increased dietary fat storage beyond about 50 g in a normal resting adult. This has important implications for 13CO2-based studies.

Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index.

BACKGROUND: Although international interest in classifying subject health status according to adiposity is increasing, no accepted published ranges of percentage body fat currently exist. Empirically identified limits, population percentiles, and z scores have all been suggested as means of setting percentage body fat guidelines, although each has major limitations. OBJECTIVE: The aim of this study was to examine a potential new approach for developing percentage body fat ranges. The approach taken was to link healthy body mass index (BMI; in kg/m(2)) guidelines established by the National Institutes of Health and the World Health Organization with predicted percentage body fat. DESIGN: Body fat was measured in subjects from 3 ethnic groups (white, African American, and Asian) who were screened and evaluated at 3 universities [Cambridge (United Kingdom), Columbia (United States), and Jikei (Japan)] with use of reference body-composition methods [4-compartment model (4C) at 2 laboratories and dual-energy X-ray absorptiometry (DXA) at all 3 laboratories]. Percentage body fat prediction equations were developed based on BMI and other independent variables. RESULTS: A convenient sample of 1626 adults with BMIs < or =35 was evaluated. Independent percentage body fat predictor variables in multiple regression models included 1/BMI, sex, age, and ethnic group (R: values from 0.74 to 0.92 and SEEs from 2.8 to 5.4% fat). The prediction formulas were then used to prepare provisional healthy percentage body fat ranges based on published BMI limits for underweight (<18.5), overweight (> or =25), and obesity (> or =30). CONCLUSION: This proposed approach and initial findings provide the groundwork and stimulus for establishing international healthy body fat ranges.

Macronutrient disposal during controlled overfeeding with glucose, fructose, sucrose, or fat in lean and obese women.

BACKGROUND: Previous short-term studies (< or =6 h) showed differences in energy expenditure (EE) and macronutrient oxidation in response to overfeeding with different types of dietary carbohydrate. This finding could have implications for obesity. OBJECTIVE: We used 96-h continuous whole-body calorimetry in 8 lean and 5 obese women to assess metabolic disposal (energy dissipation and glycogen or fat storage) of a controlled excess of dietary energy supplied as different carbohydrate sources or as fat. DESIGN: Five dietary treatments were applied in random order: energy balance (control) and overfeeding by 50% of energy requirements with fat (O(fat)) or predominantly with glucose, fructose, or sucrose (O(cho)). Macronutrient oxidation rates were assessed from nonprotein gaseous exchanges. Net macronutrient balances were calculated as cumulative differences between intake and oxidation. RESULTS: Increased EE in response to overfeeding dissipated 7.9% of the energy excess with a variation in EE of <1.7% across overfeeding treatments (NS). EE during the O(fat) treatment significantly exceeded that during the control treatment in the lean but not in the obese women. There were no significant differences between lean and obese women in macronutrient oxidation or balances, so data were pooled. O(cho) induced glycogen storage on day 1 ( approximately 100 g) but thereafter progressively stimulated carbohydrate oxidation so that balance was reached on days 3 and 4. Fat oxidation was proportionately suppressed. Of the excess carbohydrate, 74% was oxidized; there were no significant differences between the various O(cho) treatments. O(fat) stimulated fat oxidation by 18% and suppressed carbohydrate oxidation. On average, 12% of the excess energy was stored as glycogen and 88% as fat; there was no significant difference between overfeeding treatments. CONCLUSION: There was no significant difference in fat balance during controlled overfeeding with fat, fructose, glucose, or sucrose.

Evaluation of the novel Tanita body-fat analyser to measure body composition by comparison with a four-compartment model.

The Tanita body-fat analyser is a novel device to estimate body fat, based on the principles of bioelectrical impedance. It differs from other impedance systems which use surface electrodes in that the subjects stand bare-footed on a metal sole-plate which incorporates the electrodes, hence impedance is measured through the legs and lower trunk. In 104 men and 101 women (16-78 years and BMI 16-41 kg/m2) the mean bias in body-fat mass measured using the Tanita body-fat analyser was 0.8 (2SD 7.9) kg relative to a four-compartment model. This is comparable to the other prediction techniques tested (conventional tetrapolar impedance -1.3 (2SD 6.9) kg, skinfold thicknesses 0.3 (2SD 7.4) kg, and BMI-based formulas -0.2 (2SD 9.0) kg and -0.6 (2SD 8.5) kg), but the agreement was poorer than for 'reference' methods to measure body fat (density 0.2 (2SD 3.7) kg, total body water -0.9 (2SD 3.4) kg and dual-energy X-ray absorptiometry 0.1 (2SD 5.0) kg). The present paper also describes the derivation of a new prediction equation for the calculation of body composition from the Tanita body-fat analyser. The equation incorporates sex, age, and a log-transformation of height, weight and the measured impedance to predict body fat measured by a four-compartment model. This approach is recommended in the derivation of other prediction equations in body composition analysis. Using this novel prediction equation the residual standard deviations were 4.8% for men and 3.3% for women. A similar analysis using data collected with a conventional tetrapolar system yielded residual standard deviations of 4.3% for men and 3.1% for women. This demonstrates that the practical simplicity of the novel Tanita method is not associated with a clinically significant decrement in performance relative to a traditional impedance device.

Effects of inactivity and diet composition on human energy balance.

OBJECTIVES: To investigate the influences of inactivity and dietary macronutrient composition on energy and fat balance and to look for interactions between them. DESIGN: Two-day measurements of energy expenditure and substrate oxidation on five occasions; ad libitum food intake from diets of 35% and 60% energy as fat, with and without imposed activity, and a fixed overfeeding at 35% fat with free activity. SUBJECTS: Eight normal-weight male volunteers. MEASUREMENTS: Energy expenditure and substrate oxidation by indirect whole-body calorimetry, and macronutrient intakes from food consumption on ad libitum regimens. RESULTS: Subjects consumed the same energy, mean 11.6 MJ/d, regardless of activity level, on the 35% diet. Subjects consumed more energy on the 60% than the 35% diet, mean 14 vs. 11.6 MJ/d. Inactivity induced a strong positive energy balance: 5.1 (60% diet), and 2.6 MJ/d (35% diet). Energy balance with activity was not significantly different between diets, nor significantly different from zero: 1.1 MJ/d (60% diet), and -0.2 MJ/d (35% diet). When intentionally overfed, subjects failed to compensate by raising voluntary activity. CONCLUSION: Energy intake was not regulated over a 2-day period in response to either imposition of inactivity or a high-fat diet. Activity proved essential to the avoidance of significant positive energy balance.

Dietary compensation in response to covert imposition of negative energy balance by removal of fat or carbohydrate.

Compensatory changes in energy intake (EI) and macronutrient metabolism in response to modest covert underfeeding were tested by whole-body calorimetry in eight lean men. Each was studied on three occasions comprising a controlled stabilization day followed by manipulation and outcome days in a whole-body calorimeter. On the manipulation day EI was fixed, and calculated to maintain energy balance (CONTROL) or to provide 85% of CONTROL BY removing energy as carbohydrate (CHOred) or as fat (FATred). On the outcome day, ad libitum EI was allowed at fixed mealtimes. CHOred and FATred manipulations generated significantly different energy balances (-1.10 (SE 0.13) MJ, P = 0.000; -1.10 (SE 0.12) MJ, P = 0.000) and fat balances (-0.61 (SE 0.23) MJ, P = 0.03; -1.09 (SE 0.20) MJ, P = 0.000), but not carbohydrate balances (-0.39 (SE 0.22) MJ, NS; 0.11 (SE 0.23) MJ, NS) by the end of the manipulation day compared with CONTROL. On the outcome day, EI was significantly higher than CONTROL after CHOred (+1.58 (SE 0.33) MJ, P = 0.004) and FATred (+1.21 (SE 0.49) MJ, P = 0.022) with no differences between treatments. Overall 48 h energy balances averaged close to zero at -0.14, +0.34, +0.04 MJ on CONTROL, CHOred and FATred respectively. Total 48 h energy intakes on CHOred and FATred averaged 101 (SE 1.7)% and 99 (SE 2.5)% of CONTROL, thus demonstrating accurate detection of a mild energy deficit and efficient next-day compensation. Despite significant differences in macronutrient oxidation rates, the energy homeostatic mechanism appeared to be independent of specific macronutrient deficits.

Effect of dietary manipulation on substrate flux and energy balance in obese women taking the appetite suppressant dexfenfluramine.

BACKGROUND: Studies in lean men show poor regulation of energy (EB) and fat balance (FB) during manipulation of dietary ratios of fat to carbohydrate. High-fat (HF), high-energy diets cause hyperphagia and a positive EB and FB. OBJECTIVE: The protocol was designed to measure substrate flux and EB in obese women taking dexfenfluramine (DF) or placebo (PL) during an HF (50% of energy) or low-fat (25% of energy; LF) diet. We hypothesized that alterations in dietary fat would not be regulated and would lead to a positive EB and FB. DESIGN: The study was double-blind, randomized, and placebo-controlled, with 4 treatments (LF/DF, HF/DF, LF/PL, and HF/PL) and a crossover. Five days of continuous, whole-body calorimetry measurements were made in 6 subjects after 8 d of home DF/PL treatment. Macronutrient balance and EB were measured within the chamber as the cumulative difference between ad libitum intake and oxidation. RESULTS: The HF diet increased energy (HF, 10.50 MJ/d; LF, 8.13 MJ/d; P < 0.0001) and fat intakes (HF, 5.34 MJ/d; LF, 2.06 MJ/d; P < 0.0001), leading to a positive EB (delta = 2.37 MJ/d) and FB (delta = 2.31 MJ/d). DF reduced energy (DF, 8.96 MJ/d; PL, 9.66 MJ/d; P < 0.01) and macronutrient intakes, but did not increase energy expenditure (delta = -0.31 MJ/d; P < 0.01), or 24-h fat oxidation (delta = 0.03 MJ/d; P = 0.46). CONCLUSIONS: EB and FB are poorly regulated with HF, energy-dense diets in obese women, which leads to fat deposition and weight gain.

Short-term effects of alcohol consumption on appetite and energy intake.

The relationship between alcohol intake and obesity remains uncertain. Evidence suggesting that alcohol-derived energy may be unregulated points to an inability to maintain appetite, energy balance and, hence, body weight when alcohol is introduced to the diet. This study investigated the short-term effects of alcohol on hunger and energy intake in 20 lean women. On 4 occasions, subjects were given a randomised preload drink ('alcohol', 'no alcohol', 'carbohydrate', 'water') followed by visual analogue scales (VAS) rating hunger and an ad lib test meal. There was no difference in hunger ratings (p > 0.05) nor in the amount of energy consumed during the test meal (F = 1.66, p > 0.05) following any of the 4 preloads. Consumption of the 2 high energy preload drinks ('alcohol', 0.91 MJ; 'CHO', 0.72 MJ) did not result in a compensatory decrease in the amount of energy subsequently eaten (ad lib intake: 'alcohol' = 2.62 MJ, 0.32 SEM; 'no alcohol' = 2.98 MJ, 0.28 SEM; 'CHO' = 2.93 MJ, 0.21 SEM; 'water' = 2.82 MJ, 0.25 SEM), suggesting either no physiological recognition or no regulation of energy consumed within a drink in quantities of less than 1 MJ. The addition of either alcoholic or CHO-containing carbonated beverages into the diet will result, in the short-term, to an overall increase in energy intake.

Changes in macronutrient balance during over- and underfeeding assessed by 12-d continuous whole-body calorimetry.

Alterations in energy balance must be accommodated by adjustments in the net storage of the major energy-yielding macronutrients: carbohydrate, protein, and fat. This study used continuous whole-body calorimetry to measure changes in energy expenditure and substrate oxidation during a 12-d imposed energy imbalance in six lean men on mixed diets (overfeeding: 16.5 MJ/d, +33%, n = 3; underfeeding: 3.5 MJ/d, -67%, n = 3). Changes in total energy expenditure (TEE) and its components were modest; TEE changed by +6.2% (overfeeding) and -10.5% (underfeeding). In consequence, body weight changed by +2.90 and -3.18 kg. Marked changes in metabolic fuel selection occurred over the course of the study. Carbohydrate intake (540 and 83 g/d for overfeeding and underfeeding, respectively) exerted direct autoregulatory feedback on carbohydrate oxidation (551 and 106 g/d at day 12 for overfeeding and underfeeding, respectively). Subjects were close to balance by day 5. Changes in protein oxidation were small and not sufficient to prevent the oxidation of body protein mass, or its accretion, in response to energy deficit or surplus. Fat oxidation (59 and 177 g/d for overfeeding and underfeeding, respectively) was not sensitive to dietary fat intake (150 and 20 g/d, for overfeeding and underfeeding, respectively), rather, its oxidation was inversely related to the oxidation of other substrates. Changes in fat balance accounted for 74.1% and 84.0% of the energy imbalance during overfeeding and underfeeding, respectively. This study shows a clear oxidative hierarchy for the macronutrients. Metabolic fuel selection is dominated by the need to maintain carbohydrate balance. This induces inappropriate counterregulatory alterations in fat oxidation during energy surplus.

Physical activity and obesity: problems in correcting expenditure for body size.

OBJECTIVE: To explore the best method of adjusting energy expended on physical activity (AEE) for differences in body size. Many publications have expressed AEE per kg body weight (i.e. using weight 1.0 as denominator). This makes the unjustified assumption that all activities are weight-dependent. DESIGN: Retrospective analysis of data from ninety-two 24-h whole-body calorimetry measurements in women, and 574 doubly-labelled water measurements in men and women to calculate the optimal exponents of body weight for adjusting AEE. RESULTS: The analysis proved that weight 1.0 over-corrects for size differences and yields invalid conclusions about relationships between physical activity and obesity. An exponent close to 0.5 is more appropriate for sedentary lifestyles. However the correct exponent is itself dependent on the relative mix of weight-dependent and non-weight-dependent activities undertaken. CONCLUSION: We conclude that it is impossible to recommend a generalizable coefficient for adjusting AEE, and that great caution must be exercised when interpreting AEE data from individuals of markedly different body sizes.

Metabolic fuel utilisation in obese women before and after weight loss.

OBJECTIVE: To test the hypothesis that weight rebound following slimming diets may be caused by an adaptive alteration in fuel utilisation involving a suppression of fat oxidation thus favouring fat storage in adipose tissue. DESIGN: Repeat measurements before and after two 14 d cycles of controlled weight loss using a very low energy diet (1.9MJ/d). SUBJECTS: Eight moderately obese women (body weight: 85.6 +/- 10.1 kg, BMI: 31 +/- 2 kg/m2, age: 42.6 +/- 10.1 years). MEASUREMENTS: Energy expenditure and substrate balances using 24-h whole-body indirect calorimetry and naturally labelled 13C-glucose. RESULTS: Aggregate weight loss was 5.1 +/- 0.8 kg. Twenty-four hour energy expenditure declined by 12% (8359 +/- 282 to 7366 +/- 191 kJ/d, p < 0.001). Net fat utilisation was not significantly depressed (4009 +/- 366) to 3613 +/- 191 kJ/d, NS), and the proportion of energy derived from fat was unchanged at 48.0% before weight loss and 49.0% after weight loss. CONCLUSION: The well-recognised phenomenon of reduced energy expenditure is unlikely to be a major cause of weight regain. The results do not support the theory that altered fuel selection in post-obese subjects may be the cause of difficulty in maintaining weight loss.

Alcohol and the regulation of energy balance: overnight effects on diet-induced thermogenesis and fuel storage.

The effect of alcohol on overnight energy expenditure and substrate disposal was studied in eleven subjects (five men, six women) using whole-body indirect calorimetry for 15.5 h after test meals. Three test meals were studied in random order with at least 48 h between treatments: control, 50% of maintenance energy needs provided as 14, 40 and 46% energy from protein, fat and carbohydrate respectively; alcohol addition, control plus 23% energy as alcohol; alcohol substitution, control with alcohol replacing 23% of carbohydrate energy. ANOVA revealed no significant sex effects. Alcohol-induced thermogenesis dissipated only 15 (SD 14)% of the alcohol energy. Alcohol addition had no significant effect on protein or carbohydrate oxidation but fat oxidation was suppressed (P < 0.0005) to an extent equivalent to storing 74 (SD 51)% of the alcohol energy as fat. Alcohol substitution reduced carbohydrate oxidation (P < 0.009) to an equivalent of 42 (SD 41)% and also spared fat (P < 0.005) to an equivalent of 59 (SD 37)% of the alcohol energy. It is concluded that alcohol has no special thermogenic capacity, and that its energy can be accounted for in a similar way to carbohydrate.

Effects on metabolic rate and fuel selection of a selective beta-3 agonist (ICI D7114) in healthy lean men.

METHOD: ICI D7114 is a selective beta-3 agonist which in some animals increases metabolic rate, promotes weight loss and improves glucose tolerance. To investigate its potential usefulness in humans, 16 healthy young men (mean age 28.9 +/- 8.0 years; body mass index 22.5 +/- 1.6 kg/m2) were given ICI D7114 (150 mg/day, 2.08 +/- 0.24 mg/kg body weight) or placebo for 14 days in a double-blind randomised parallel group trial. Energy expenditure (EE) and substrate oxidation were assessed by continuous whole-body indirect calorimetry on Day 0 (before dosing), on day 1 (acute effect) and on Day 14 (chronic effect). RESULTS: Analysis of covariance indicated no significant effects on EE 4 h post-dose (Day 1, +2.4%, NS; Day 14, +1.0%, NS). There was no chronic effect on either the lowest 1 h of sleeping EE (+2.2%, NS) or 24 h EE (+0.7%, NS). There was a marginally significant chronic stimulation of basal metabolic rate (+3.6%, P = 0.042). ICI D7114 had no significant influence on protein, fat or carbohydrate oxidation. Tolerability and safety data showed that there were no increases in resting heart rate or blood pressure; no change in plasma potassium or reports of tremor; no haematological or biochemical abnormalities and no adverse events. CONCLUSION: We conclude that over 14 days ICI D7114 at a dose level of 150 mg/day has no biologically significant effect on EE in healthy, lean men.