Long-term measurements of energy expenditure in humans using a respiration chamber13

Transcription

1 Long-term measurements of energy expenditure in humans using a respiration chamber13 Eric J#{233}quier,MD and Yves Schulz, PhD Introduction ABSTRACT There is a need to measure energy expenditure in man for a period of 24 h or even several days. The respiration chamber offers a unique opportunity to reach this goal. It allows the study of energy and nutrient balance: from the latter. acute changes in body composition can be obtained. The respiration chamber built in Lausanne is an air-tight room (5 m long. 2.5 m wide, and 2.5 m high) which forms an open circuit ventilated indirect calorimeter. The physical activity of the subject inside the chamber is continuously measured using a radar system based on the Doppler effect. Energy expenditure of obese and lean women was continuously measured over 24 h and diet-induced thermogenesis was assessed by using an approach which allows one to subtract the energy expended for physical activity from the total energy expenditure. Expressed in absolute terms, total energy expenditure was more elevated in the obese than in the lean controls. Basal metabolic rate was also higher in the obese than in the controls, but diet-induced thermogenesis was found to be blunted in the obese. In a second study. the effect of changing the carbohydrate/lipid content of the diet on fuel utilization was assessed in young healthy subjects with the respiration chamber. After a 7-day adaptation to a highcarbohydrate low-fat diet, the fuel mixture oxidized matched the change in nutrient intake. A last example of the use of the respiration chamber is the thermogenic response and changes in body composition due to a 7-day overfeeding of carbohydrate. Diet-induced thermogenesis was found to be 27%: on the last day ofoverfeeding. carbohydrate balance was reached by oxidation of 5% of the carbohydrate intake, the remaining 5% being converted into lipid. Am J Cli,, Nutr 1983:38: KEY WORDS Metabolic rate, energy expenditure. nutrient balance, obesity Despite a large number of studies on human energy expenditure, it is not clearly established how much food man requires (1, 2) since continuous measurements of energy expenditure in man over 24-h periods have been seldom undertaken. It is noteworthy that most studies on energy expenditure have been performed over short periods of 2 to 4 h (3-1). Extrapolation of these data to energy expenditure over 24 h or several days is open to question since energy expenditure markedly changes with activity, after meals, and during sleep (1 1). Therefore, there is a need to measure energy expenditure continuously for periods of 24 h or several days, in order to assess human energy requirements more precisely (12). It is not intended here to review the literature on long-term energy expenditure measurements in man; the aim of this presentation is to summarize our own 4-yr experience of long-term measurements of energy expenditure using a respiration chamber. The respiration chamber offers a unique opportunity to study two important aspects of energy metabolism in humans ie, 1 ) energy balance and 2) nutrient balance; from the latter, acute changes in body composition can be obtained. A method to study energy balance An individual with stable body weight and body composition is in energy balance, I From the Institute of Physiology, Faculty of Mcdicine, University of Lausanne, Laussane, Switzerland. 2 Supported by a research grant of the Nestl#{233} Cornpany. I 8 Vevey. Switzerland. 3 Address reprint requests to: Professor Eric J#{233}quier, Institute of Physiology, University of Lausanne. Rue du Bugnon 7, CH-lOl I Lausanne. Switzerland. The American Journal ofclinical Nutrition 38: DECEMBER 1983, pp Printed in USA 1983 American Society for Clinical Nutrition 989

2 99 JEQUIER AND SCHUTZ which means that within a given period of time energy expenditure matches energy intake. Energy balance studies provide useful information concerning the energy requirements of obese and lean individuals under standardized living conditions (1 1). In addition to energy balance studies which aim at assessing the energy requirements of various individuals, it is also ofinterest to study the adaptive response, ie, the magnitude of changes in energy expenditure in regard to alterations in energy intake (1 3). The study of thermogenesis in man is of great interest since animal models of genetic obesity exhibit a reduced thermogenic response to increased energy intake (14, 15) a condition that favors energy retention and weight gain. A method to assess acute changes in body composition By simultaneously measuring oxygen consumption (VO2) carbon dioxide production (VCO2) and urinary nitrogen excretion, it is possible to compute the utilization rate of carbohydrates, lipids, and proteins (12). With a knowledge of the nutrient composition of the diet and the 24-h nutrient utilization, the net balance demonstrates acute changes in body composition. A correction can be made for the nonabsorbed nutrients by measuring the nutrient content in the feces, or a factor for computing metabolizable energy can be used, since the digestibility of nutrients is fairly constant in individuals without gastrointestinal diseases. It is important to understand that by using the technique of indirect calorimetry it is possible to determine the net rate of nutrient utilization, even in the presence of lipogenesis from carbohydate (16). When the respiratory quotient corrected for protein metabolism, ie, the nonprotein respiratory quotient, has a value between.7 and 1., this indicates that the rate of lipid oxidation, is greater than that of lipogenesis from carbohydrate; the amount of lipid oxidized obtamed by indirect calorimetry represents the net balance between these two processes. When the nonprotein respiratory quotient is more than 1., then net lipogenesis does occur (ie, the total rate of lipogenesis is greater than that of lipid oxidation). Thus respiratory exchange measurements give the net lipid balance which corresponds to the difference between the rate of lipogenesis and that of lipid oxidation. Under conditions of continuous measurements of VO2 and VCO2, the influence of unsteady ventilation on respiratory quotient is cancelled, since only mean values for periods of 15 or 3 mm are considered; therefore, if transient hyperventilation occurs, it is necessarily followed by a compensatory hypoventilation, and the mean 3-mm values ofvo2 and VCO2 reflect the true oxygen consumption and carbon dioxide production, respectively. It must be pointed out however that respiratory exchange measurements from which nutrient utilization can be computed cannot be performed on patients with changes in acid-base status, which obviously lead to alterations in the blood CO2 content and affect VCO2 measurements. Description of the respiration chamber The respiration chamber (12, 17) built in Lausanne, is an air-tight room (5 m long, 2.5 m wide, and 2.5 m high) which forms an open circuit ventilated indirect calorimeter (Fig 1). Outside air is continuously drawn into the chamber and the flow rate of air at the outlet is measured using a pneumotachograph with a differential manometer (Digital Pneumotachograph, model 4733 H, Hewlett Packard). A fraction of the extracted air is continuously analyzed for 2 and CO2 concentrations with a thermomagnetic 2 analyzer (Magnos 2T, full scale 19 to 2 1 %, Hartmann and Braun, Frankfurt, Germany) and an infrared CO2 analyzer (Uras 2T, full scale to 1%, Hartmann and Braun). These analysers are calibrated twice a day using a gas mixture prepared immediately with a proportional mixing pump (H Wosthoff, Bochum, Germany). Air flow rate, 2 and CO2 concentration of outfiowing air are computed on line to obtam VO2, VCO2 (under STPD conditions), respiratory quotient, and consequently energy expenditure using the equations previously described (12). The mean values of these parameters are printed at 15- or 3- mm interval. Values of energy expenditure

3 ENERGY EXPENDITURE IN HUMANS USING RESPIRATION CHAMBER 991 L o2f/ FIG 1. Diagram of the respiration chamber. Ambient air (F1O2, FCO2) is drawn into the air-tight chamber, air is extracted from the chamber by a pump and the air flow (V) is measured by a pneumotachograph. At the outlet, air is continuously analysed for 2 (F,,,,O2) and for CO2 (F1CO2). and nutrient oxidation rates are integrated for 24 h to compute energy balance and changes in body composition. In our chamber, the expiratory gases from the subject are rapidly mixed with the total air volume of the chamber; therefore, the concentrations of 2 and CO2 at the outlet of the chamber are equal to their respective mean concentration in the chamber. The mixing of expiratory gases with air is accelerated by using several small blowers inside the chamber, which results in a response time of approximately 2 to 3 mm to a step change (for example the beginning of an exercise at a constant load). The accuracy ofthe measurements of VO2 and VCO2 was assessed by burning butane inside the chamber. In 14 calibration tests of 1 h each, the measured V2 was 1.44 ±.34% ofthe real V2 obtained by weighing the amount of butane which had been burnt and by stoichiometric calculation of the volume of 2 utilized; the measured VCO2 was ±.5% of the real VCO2. Thus, the respiration chamber is a very accurate instrument for measuring both VO2 and VCO2 since the error of both measurements is within ±2%. Assessment of physical activity within the chamber A radar system, based on the Doppler effect, is used to continuously assess the spontaneous physical activity of a subject living in a respiration chamber (1 8). The unit (Zettler GHz-Doppler Mime 15, MUnchen, Germany) continuously emits a constant radar signal into the chamber, which is reflected by the walls of the chamber and objects within it. A radar receiver, working on the Doppler principle has been tuned to detect any movement within the chamber at a speed higher than 75 mm/s. The receiver is linked to a data acquisition system (Hewlett Packard 352A and 9825) which records the integrated value given by the receiver and resets the integrator each minute. The final output gives the percentage of time during which the subject is active. It is however not possible to record the intensity of the activity; thus, the system gives an overall index of physical activity in a semiquantitative manner. A validation of the procedure is given by plotting the mean 15-mm VO2 measurements against the percentage activity in subjects under ad libitum

4 992 JEQUIER AND SCHUlZ conditions of activity: a linear relationship (p <.1) is obtained between VO2 and percentage activity (Fig 2). In each subject studied in the chamber, the individual regression lines were all statistically highly significant. Measurement of the overall diet-induced thermogenesis The intercept at zero activity level on the ordinate of the regression line VO2 versus percentage activity (Fig 2) represents the mean resting metabolic rate (RMR) ie, the sum of basal metabolic rate (BMR) and the overall diet-induced thermogenesis (DIT). DIT is often expressed as a percentage of the energy content of the meal (ECM) and is calculated as follows:.! 3 (RMR - BMR) DIT=#{176}t.1 ECM where -t (RMR - BMR) represents the integration of the increase in metabolic rate due to food ingestion from time (meal ingestion) to time t (end ofthe thermic effect of the meal). A validation ofthis approach for assessing DIT is to compare the energy expenditure obtained during a day with usual food intake V2 %i.ctmty (radar) FIG 2. Regression lines between the percent activity measured by radar (Doppler effect) and the oxygen consumption (V2) in mi/mm. Each line was obtained by plotting mean I 5-mm values ofactivity and V2 for 5 h. The upper line (feeding) was obtained in four subjects after a meal, whereas the lower line (fasting) was obtained in the same subjects on a different day without any food intake. The interval between the two lines represents the effect of DIT. The level of BMR is indicated on the ordinate. it s value is close to the intercept at zero activity level of the fasting line. with that of a fasting day (Fig 2); in the latter, the intercept of the regression line (VO2 versus percentage activity) at % activity gave a value similar to BMR measured under standardized conditions, and therefore DIT was found to be essentially zero. Consequently, on a day with food intake, the difference between the intercept at % activity of the regression line ( freding line, Fig 2) and the BMR mainly represents dietinduced thermogenesis. Examples of investigations using a respiration chamber Energy balance in obesity Our knowledge of overall energy expenditure during 24 h (24-EE) in lean and obese subjects is very limited (1 1, ). It is of great interest to study 24-EE under standardized conditions of feeding in individuals with marked differences in body weight in order to investigate whether a low energy expenditure could contribute to the energy imbalance which leads to obesity. BMR is elevated in obese individuals when compared to lean controls (1 1, 22-26); this is likely to be due to the greater lean body mass of obese individuals than that of sedentary lean controls, since BMR is highly correlated with the size of the lean body mass (1 1, 24, 25). DIT in obese subjects has been described to be lower than that of lean individuals (4, 6, 8, 23, 27, 28), but some reports have failed to show differences in DIT between obese and lean subjects (9, 1, 29). Although the reason for this discrepancy is not yet understood, it is important to realize that most studies on DIT have been conducted over periods of 2 to 3 h only. Since the thermogenic response to a meal is usually not terminated after this period of time (3), it is likely that the total response was not measured, and the question arises whether the low DIT reported in obese subjects might simply reflect a delayed thermogenic response. In order to study this question, the overall DIT to three meals was investigated in eight lean and 2 obese young women with a childhood history of obesity over 15 h using the respiration chamber and the method of individual regression lines between VO2 and

5 ENERGY EXPENDITURE IN HUMANS USING RESPIRATION CHAMBER 993 percentage activity described above. The 24- h energy intake was tailored to the size of the fat free mass (FFM), (4 1.5 kcal/kg FFM). The results are summarized in the Table 1: DIT, expressed as a percentage ofthe energy content of the meals was significantly lower in the obese (8.7 ±.8%) than in the lean control women (14.8 ± 1.1%, p <.1). These results support the concept of a thermogenic defect in obese women which is not compensated for by a more prolonged response. In this study, BMR of the obese (1. 19 ±.3 kcal/min) was significantly greater than that of lean controls (.88 ±.3 kcal/min, p <. 1), which confirms other reports (1 1, 22-29). The energy expenditure due to BMR and DIT together was also greater in the obese (1.4 ±.4 kcal/min) than in the controls ( ±.3 kcal/min, p <.5). This shows that the low DIT in the obese does not compensate for their large BMR. These results are in agreement with previous reports (4, 6, 8, 23, 27, 28) which have described a defective thermogenesis in obese with a childhood history of obesity, but the resting metabolic rate (including DIT) of obese was greater than that of controls. It is important to establish whether this thermogenic defect in obese with a childhood history of obesity is still present after weight loss. In a recent study (3 1), we found that the reduced DIT in a group of obese women (mean body weight 85 ± 3 kg) was not normalised after a mean weight loss of 12 kg due to a hypocaloric diet. Although the patients after weight loss were still moderately obese, it is noteworthy that the thermogenic defect was unaffected by the change in body weight. These results suggest that the thermogenic defect in the obese is not a consequence of the increased body weight. It is possible that during the dynamic phase ofobesity (ie, during the weight gain period), a defective capacity to adapt energy expenditure to a variable energy intake may be a factor favouring energy retention. Further investigations are needed to study this possibility. It has often been reported that obese individuals can maintain their body weight with a reduced daily caloric intake (32) when compared to recommended dietary allowances. Our measurements of energy expenditure during 24 h in the respiration chamber in obese patients do not support this concept. Under conditions ofad libitum activity in the chamber, obese individuals expend more energy than lean controls, and there is a significant linear relationship between body weight and 24-h energy expenditure (Fig 3). The high energy expenditure in the obese is mainly due to a greater basal metabolic rate than that oflean controls (1 1,22-29). The results oftotal 24-h energy expenditure show that under the artificial life conditions of a respiration chamber, the energy requirements of the obese are greater than that of lean individuals. It is not possible, however, to extrapolate these data to the everyday life conditions where physical activity is more variable than in the restricted environment of a respiration chamber. The fact that obese subjects expend more energy in a respiration chamber than lean controls does not allow us to conclude that hyperphagia is the necessary mechanism which has induced obesity. The fact that a thermogenic defect is present in the obese after weight loss (3 1) suggests that a reduced thermogenic capacity can play a role favouring weight gain in the preobese state (33- TABLE 1 Physical characteristics oflean and obese women: BMR, and DIT resulting from three meals measured over 15 h n Age yr Body kg wt BMR keal/inin BMR + DIT Lean 8 24± 1 55± ± ± ± 1.1 Obese 2 3 ± 2 88 ± ±.3t 1.4 ±.4f 8.7 ±.8t * Increase in energy expenditure over BMR expressed as percentage of the overall energy intake. t p <.1. p<.5. kcai/,nin DIT %

6 994 JEQUIER AND SCHUlZ KcaI I 24h 35 I-. La Li LI 1 5 I I I I I I I I I I BODY WEIGHT Kg FIG 3. Relationship between body weight and total 24 h energy expenditure in 48 lean and obese women (r =.86, p <.1). 35). The increased body weight in the obese consists mainly offat, but also in a moderate increase of lean body mass; it is known that the latter results in an elevated basal metabolic rate (1 1, 24, 25, 29). Thus, weight gain may be easily induced in individuals with a low thermogenic response after food ingestion; then, the rise in basal metabolic rate compensates for the low diet-induced thermogenesis, and eventually total energy expenditure becomes even greater than in the preobese state (33). According to this concept, body weight stabilizes in the obese at a steady state level which is reached when the overall 24-h energy expenditure matches the mean daily energy intake (33). Since the thermogenic capacity in the obese (with a metabolic propensity toward obesity) is defective, energy balance is reached at a higher body weight than in individuals with an unaltered thermogenesis. The large body weight in the obese can be considered to be a compensated state in which the energy intake is dissipated due to an elevated basal metabolic rate (33, 35). A similar concept applies to obviously hyperphagic obese individuals in whom the increased energy intake is the cause of obesity. In these patients body weight also stabilizes at a level above normal, which allows to dissipate the excess energy intake as heat, thanks to an elevated basal metabolic rate. Thus the hyperphagic obese patient eventually reaches a stable body weight which corresponds to energy balance with both high input and high output. Effect ofa change in carbohydrate/lipid intake on fuel utilization In addition to energy balance studies measurements of nutrient balance are of great interest. The relationship between dietary composition and the fuel mixture oxidized over 24 h has received little attention (36). As mentioned previously, continuous measurement of V2, VCO2, and urinary nitrogen excretion permits the calculation of the fuel mixture oxidized and the nutrient balance if we know the amount of ingested nutrients.

7 ENERGY EXPENDITURE IN HUMANS USING RESPIRATION CHAMBER z I V The dietary composition markedly influ- of 76 ± 3 g/24 h of lipid (Fig 4). These ences the substrates oxidized over 24 h as changes in the composition of the diet were illustrated by the following example (17). very well matched by similar modifications Eleven healthy medical students (six females in the substrates which were oxidized, ie, an and five males) were adapted for 7 days increase of 194 ± 1 5 g/24 h of carbohydrate to a maintenance mixed diet [carbohy- oxidized, and a decrease of 7 ± 1 1 g/24 h drate(cho): 43%, lipid: 4%, and protein: oflipid oxidized (Fig 4). Thus, with a main- 1 7% kcal] and the last day was spent in the tenance diet, the fuel mixture oxidized over respiration chamber to measure substrate 24 h is closely related to the composition of balances. They were then adapted for 7 days the ingested nutrients; the intake of a large to a high-carbohydrate low-fat diet (CHO: amount of carbohydrate stimulates their 77%, lipid 5%, and protein: 18% kcal) and own oxidation rate. This is in keeping with the last day was again spent in the respiration the limited capacity of storing carbohydrate chamber. The changes in nutrients intake (16). from the mixed to the high-carbohydrate As a result of the adaptation of the fuel low-fat diet consisted in an increase of 178 mixture oxidized to the composition of the ± S g/24 h of carbohydrate and a decrease diet, there was no change in body composig, 24h ( + bc 5-5 PROTEIN LIPID CHO z 4 * z +6 z 4 I V - 1( FIG 4. Eleven subjects were adapted for 7 days to a mixed diet. Then a high-carbohydrate low-fat diet was given during a 7-day period. The upper part of the figure shows the change in nutrient intake (g/24 h) between the mixed and the high-carbohydrate low-fat diet. The lower part of the figure shows the change in substrate oxidation (g/24 h) after 7 days of adaptation to the high-carbohydrate low-fat diet. Note that the changes in nutrient oxidation matches the changes in nutrient intake.

8 996 JEQUIER AND SCHUTZ tion due to the high-carbohydrate low-fat diet. It is not yet established whether a high proportion of fat in the diet promotes lipid oxidation. It would therefore be interesting to study if a high-fat low-carbohydrate diet induces more fat oxidation than a mixed diet. The following example illustrates acute changes in body composition during a short period of overfeeding. Assessment ofthe thermogenic capacity and ofacute changes in body composition during carbohydrate overfteding in man Diet-induced thermogenesis is generally assumed to represent about 1% of the energy intake. However, this value can be markedly increased when energy intake surpasses the energy requirements. A recent O/24h I-- overfeeding study (1 3) was performed in three young adult males with an excess of carbohydrate intake during 7 days (the daily energy intake was calculated to be approximately 15 kcal in excess of the previous days energy expenditure). The diet-induced thermogenesis due to overfeeding was found to be 27 ± 1%, which means that 27% of the excess energy intake (over basal energy requirements) was oxidized, the remainder being stored as glycogen and fat. This value of DIT is much greater than that previously reported and illustrates the fact that the thermogenic capacity in young adult man is able in part to limit the excess of energy being stored during overfeeding. The changes in body composition were determined by computing the daily nutrient balance. Figure 5 shows carbohydrate and lipid balances measured on the 7th day of -I- -L- /24h 2 CHO CHO CHO INTAKE METABOLIZEDOXIDIZED CHO - LIPID I 1 CHO BALANCE -I I LIPID LIPID NET LIPID INTAKE OXIDIZED LIPOGENESIS BALANCE FIG 5. CHO and lipid metabolism on the 7th day of a CHO overfeeding period. CHO metabolized includes CHO oxidized and CHO converted into lipid. CHO balance is almost reached, whereas lipid balance is markedly positive due to a large net lipogenesis.

9 ENERGY EXPENDITURE IN HUMANS USING RESPIRATION CHAMBER 997 the overfeeding period. Carbohydrate intake was 173 ± 25 g/24 h and the amount of CHO metabolized was 1 18 ± 3 g/24 h, which illustrates almost perfect CHO balance despite the enormous CHO intake. Carbohydrate metabolism included 526 ± 42 g/24 h of CHO oxidation and 492 ± 21 g/24 h of CHO converted into lipid. Thus about 5% of the CHO intake was used as substrate for de novo net lipogenesis, the remaining 5% being oxidized. It is worth emphasizing that CHO balance was reached after 7 days of overfeeding, which is best explained by overall glycogen stores being fully saturated and therefore obligatory metabolism of ingested CHO toward either oxidation or lipogenesis. On the 7th day of overfeeding, lipid balance was markedly positive ( ± 7 g/24 h), which was mainly due to de novo lipogenesis (156 ± 7 g/24 h), while lipid intake amounted to 17 ± 2 g/24 h only. The enormous amount oflipid synthesized over 24 h must result from a near maximum rate of lipid synthesis due to the exceptional conditions of CHO overfeeding. In conclusion, the respiration chamber is an accurate method to measure energy and nutrient balances and to study adaptive thermogenesis in man. It is a useful tool to assess the role of thermogenesis in the regulation of body weight. Further work is needed to investigate the influence ofa thermogenic defect during the dynamic phase of weight gain in obese individuals. Another field of interest is the energetic cost of pregnancy and lactation which is presently under investigation. The major advantage of the respiration chamber over other procedures (12) is the fact that the subject is unrestrained and can move freely within the chamber during the measurements. The only limitation is the artificial conditions of living in a closed environment. It is interesting to be able to assess the difference between the energy expenditure ofeveryday life and that measured within the chamber. The use of the continuous measurement of heart rate within the chamber allows one to establish individual regression lines between heart rate and enery expenditure (37). Then, continuous measurements of heart rate in everyday life can be used to indirectly assess energy expenditure from the previously established regression line. The authors thank Dr K Acheson for his contribution to the studies with the respiration chamber. References I. Durnin JVGA, Edholm G. Miller DS, Waterlow JC. How much food does man require? Nature 1973:242: Edholm G. Adam JM, Healy MJR, Wolff HS, Goldsmith R. Best 1W. Food intake and energy expenditure of army recruits. Br J Nutr I 97: 24: Pittet Ph, Gygax PH, J#{233}quierE. Thermic effect of glucose and amino acids in man studied by direct and indirect calorimetry. Br J Nutr 1974:31: Kaplan ML. Leveille GA. Calorigenic response in obese and nonobese women. Am J Clin Nutr 1976:29: Welle 5, Lilavivathana U, Campbell G. Increased plasma norepinephrine concentrations and metabolic rates following glucose ingestion in man. Metabolism 198:29: Shetty PS, Yung RT, James WPT. Barrand MD, Callingham BA. Postprandial thermogenesis in obesity. Clin Sci 1981:6: Welle S. Lilavivat U. Campbell RG. Thermic effect of feeding in man: increased plasma norepinephrime levels following glucose but not protein or fat consumption. Metabolism 1981:3: Schwartz RS, Halter JB, Bierman E. Reduced thermic effect of feeding in obesity: role of norepinephrine. Metabolism 1983:32: Welle SL, Campbell RG. Normal thermic effect of glucose in obese women. Am J Clin Nutr 1983: 37: Sharief NN. Macdonald I. Differences in dietaryinduced thermogenesis with various carbohydrates in normal and overweight men. Am J Clin Nutr 1982:35: Ravussin E, Burnand B, Schutz Y, J#{233}quierE. Twenty-four-hour energy expenditure and resting metabolic rate in obese, moderately obese, and control subjects. Am J Clin Nutr 1982:35: J#{233}quierE. Long-term measurement of energy expenditure in man: direct or indirect calorimetry. In: BjOrntorp P, Cairella M, Howard AN, eds. Recent advances in obesity research III. London: John Libbey, 198 1: Schutz Y, Acheson K, Bessard T, J#{233}quierE. Effect of a 7-day carbohydrate (CHO) hyperalimentation on energy metabolism in healthy individuals. Clin Nutr 1982:1(suppl 75Xabstr). 14. Thurlby PL, Trayhurn P. The role of thermoregulatory thermogenesis in the development of obesity in genetically obese (ob/ob) mice pair-fed with lean siblings. Br J Nutr 1979:42: Case JE, Powley IL. Development of obesity in diabetic mice pair-fed with lean siblings. J Comp Physiol Psychol 1977:91: Acheson KJ, Flatt JP, J#{233}quierE. Glycogen synthe-

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