No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Weekly Changes in Basal Metabolic Rate with Eight Weeks of Overfeeding
Abstract
The contribution of basal metabolic rate (BMR) to weight gain susceptibility has long been debated. We wanted to examine whether BMR changes in a linear fashion with overfeeding. Our hypothesis was that BMR does not increase linearly with 1000-kcal/d overfeeding in lean healthy subjects over 8 weeks. The null hypothesis states that BMR increases linearly with 1000-kcal/d overfeeding in lean healthy subjects.
Initially, 16 lean healthy sedentary subjects completed 2 weeks of weight maintenance feeding at the General Clinical Research Center. The subjects were then overfed by 1000 kcal/d over 8 weeks. BMR was measured under standard conditions each week using indirect calorimetry.
Baseline BMR was 1693 +/- 154.5 kcal/d. BMR increased from 1711 +/- 201.3 kcal/d at week 1 of overfeeding to 1781 +/- 171.65 kcal/d at the second week of overfeeding (p = 0.05). BMR fell during the third week of overfeeding to 1729 +/- 179.5 kcal/d (p = 0.05). After 5 weeks of overfeeding, BMR reached a plateau. Thereafter, there was no further change. Comparison of BMR with weeks of overfeeding was significantly different compared with the linear model (p < 0.05).
Increases in BMR in lean sedentary healthy subjects with 1000-kcal/d overfeeding are not linear over 8 weeks. There seems to be a short-term increase in BMR in the first 2 weeks of overfeeding that is not representative of longer-term changes.
... Diaz et al performed the measurements after 12.5 h and Ravussin et al after 14 h. Harris et al (37) recorded weekly changes in BMR during 8 wk of overfeeding. BMR increased over the first 2 wk, decreased in the third week, and increased and reached a plateau after 5 wk (37). ...
... Harris et al (37) recorded weekly changes in BMR during 8 wk of overfeeding. BMR increased over the first 2 wk, decreased in the third week, and increased and reached a plateau after 5 wk (37). In that study, BMR was measured ,10 h from the last meal. ...
There is a lack of appetite studies in free-living subjects supplying the habitual diet with either sucrose or artificially sweetened beverages and foods. Furthermore, the focus of artificial sweeteners has only been on the energy intake (EI) side of the energy-balance equation. The data are from a subgroup from a 10-wk study, which was previously published.
The objective was to investigate changes in EI and energy expenditure (EE) as possible reasons for the changes in body weight during 10 wk of supplementation of either sucrose or artificial sweeteners in overweight subjects.
Supplements of sucrose-sweetened beverages and foods (2 g/kg body weight; n = 12) or similar amounts containing artificial sweeteners (n = 10) were given single-blind in a 10-wk parallel design. Beverages accounted for 80% and solid foods for 20% by weight of the supplements. The rest of the diet was free choice. Indirect 24-h whole-body calorimetry was performed at weeks 0 and 10. At week 0 the diet was a weight-maintaining standardized diet. At week 10 the diet consisted of the supplements and ad libitum choice of foods. Visual analog scales were used to record appetite.
Body weight increased in the sucrose group and decreased in the sweetener group during the intervention. The sucrose group had a 3.3-MJ higher EI but felt less full and had higher ratings of prospective food consumption than did the sweetener group at week 10. Basal metabolic rate was increased in the sucrose group, whereas 24-h EE was increased in both groups at week 10. Energy balance in the sucrose group was more positive than in the sweetener group at the stay at week 10.
The changes in body weight in the 2 groups during the 10-wk intervention seem to be attributable to changes in EI rather than to changes in EE.
... TEE TEE is stimulated with overfeeding (by~10%) 9 but does not increase linearly with weight gain. 10 The extent of TEE stimulation during overfeeding governs the amount of excess energy stored and thus associated weight gain: individuals with a lesser tendency to gain weight increase TEE to a greater extent. With ensuing weight gain, resting metabolic rate will further increase (related to increased body mass) with recalibration dependent upon the relative changes in adipose tissue volume vs muscle mass (skeletal muscle has higher relative energy requirements relative to adipose tissue). ...
Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease. Similar mechanistic considerations underpinning the heterogeneity of overfeeding responses are pertinent in understanding emerging metabolic phenotypes e.g. metabolically unhealthy normal weight and metabolically healthy obesity. Intrinsic and extrinsic factors modulate individuals' overfeeding response: intrinsic factors include gender/hormonal status, genetic/ethnic background, baseline metabolic health and cardiorespiratory fitness; extrinsic factors include macronutrient (fat vs carbohydrate) content, fat/carbohydrate composition and overfeeding pattern. Subcutaneous adipose tissue (SAT) analysis, coupled with metabolic assessment, with overfeeding have revealed how SAT remodels to accommodate excess nutrients. SAT remodelling occurs either by hyperplasia (increased adipocyte number) or by hypertrophy (increased adipocyte size). Biological responses of SAT also govern the extent of ectopic (visceral/liver) triglyceride deposition. Body composition analysis by DEXA/MRI have determined the relative expansion of SAT (including abdominal/gluteofemoral SAT) versus ectopic fat with overfeeding. Such studies have contributed to the adipose expandability hypothesis whereby SAT has a finite capacity to expand (governed by intrinsic biological characteristics) and once capacity is exceeded ectopic triglyceride deposition occurs. The potential for SAT expandability confers protection from/predisposes to the adverse metabolic responses to over-feeding. The concept of a personal fat threshold suggests a large inter-individual variation in SAT capacity with ectopic depot expansion/metabolic decompensation once one's own threshold is exceeded. This review summarises insight gained from overfeeding studies regarding susceptibility to obesity and related complications with nutrient excess.
... short-term (2-7 days) overfeeding leads to weight gain (+0.5 -1.8 kg) and increased RMR (+1.1 -11.7%) (Harris et al., 2006). We have now established that, under ad libitum feeding conditions, chronic sleep restriction leads to increased caloric intake (+500 kcal) during extended wakefulness (Spaeth et al., 2013) and weight gain (+1.12 kg), but decreased RMR (-2.3%) the following day. ...
Habitual short sleep duration is consistently associated with weight gain and increased risk for obesity. The objective of this dissertation was to elucidate how chronic sleep restriction impacts components of energy balance, namely, weight gain, energy intake, and energy expenditure. Healthy adults (21-50 y) participated in controlled isolated laboratory protocols for 14-18 days and were randomized to either an experimental condition (baseline sleep followed by sleep restriction [5 consecutive nights of 4 hours time-in-bed [TIB] per night] and recovery sleep) or control condition (no sleep restriction: 10 hours TIB per night for all nights). Sleep-restricted subjects exhibited significant weight gain, increased caloric intake, greater consumption of fat, delayed meal timing and decreased resting metabolic rate (the largest component of energy expenditure) during sleep restriction but these changes returned to baseline levels after one night of recovery sleep (12 hours TIB). Control subjects did not exhibit a significant change in weight, caloric intake or resting metabolic rate across corresponding protocol days. Notably, there were significant gender and race differences in the energy balance response to sleep restriction. Men gained more weight, increased caloric intake to a greater degree during sleep restriction and consumed a larger percentage of calories during late-night hours than women. Relative to Caucasians, African Americans consumed a comparable amount of calories during baseline and sleep restriction but exhibited marked energy expenditure deficits after baseline sleep, sleep restriction and recovery sleep, and gained more weight during the study. In the largest, most diverse healthy sample of adults studied to date under controlled laboratory conditions, sleep restriction promoted weight gain and positive energy balance. Collectively, these results highlight the importance of obtaining sufficient sleep for regulating energy balance and maintaining a healthy weight, particularly in men and African Americans.
... Previous research has found that under non-sleep restriction conditions, short-term (2-7 days) overfeeding leads to weight gain (10.5-1.8 kg) and increased RMR (11.1-11.7%) (34,35). In the current study, food/drink was ad libitum. ...
Objective:
Short sleep duration is a significant risk factor for weight gain, particularly in African Americans and men. Increased caloric intake underlies this relationship, but it remains unclear whether decreased energy expenditure is a contributory factor. The current study assessed the impact of sleep restriction and recovery sleep on energy expenditure in African American and Caucasian men and women.
Methods:
Healthy adults participated in a controlled laboratory study. After two baseline sleep nights, subjects were randomized to an experimental (n = 36; 4 h sleep/night for five nights followed by one night with 12 h recovery sleep) or control condition (n = 11; 10 h sleep/night). Resting metabolic rate and respiratory quotient were measured using indirect calorimetry in the morning after overnight fasting.
Results:
Resting metabolic rate-the largest component of energy expenditure-decreased after sleep restriction (-2.6%, P = 0.032) and returned to baseline levels after recovery sleep. No changes in resting metabolic rate were observed in control subjects. Relative to Caucasians (n = 14), African Americans (n = 22) exhibited comparable daily caloric intake but a lower resting metabolic rate (P = 0.043) and higher respiratory quotient (P = 0.013) regardless of sleep duration.
Conclusions:
Sleep restriction decreased morning resting metabolic rate in healthy adults, suggesting that sleep loss leads to metabolic changes aimed at conserving energy.
... Within 24 hours of being put on the high calorie diet, the increases in VO 2 and decreases in RER of lean mice with barely detectable tumors were highly prognos-ticative of cancer aggressiveness and final tumor burden. It has been found that overfeeding also causes the resting metabolic rate of lean humans to increase rapidly [37], so this finding may be translatable to humans. ...
Obesity is associated with an increased risk of mortality from certain types of cancer, including cancer of the breast. Because obesity is associated with multiple risk factors, however, the exact reasons remain unclear. The objective of this study was to determine which of the risk factors associated with obesity are related to enhanced tumor development. The MMTV-PyMT mouse model develops mammary tumors which share numerous characteristics with those of humans. We challenged these mice with a high fat/high carbohydrate, high caloric (HC) diet, and looked for relationships between enhanced primary tumor development and adiposity, various aspects of glucose homeostasis, and metabolic factors. The HC diet enhanced tumor progression in PyMT mice. While mice on the HC diet also developed increased adiposity, hyperglycemia and hyperinsulinemia, none of these risk factors was found to be associated with the observed increases in tumor growth. Rather, we found that while overall, tumor growth was enhanced in HC diet-fed mice compared to those maintained on a regular diet, it was attenuated in individuals by an HC diet-induced increase in metabolic rate and decrease in respiratory exchange ratio. Tumor size in HC diet-fed mice was directly related to p38 phosphorylation and Bcl-2 inhibition, and the degree of vascularization of these tumors was closely and indirectly related to the rate of mouse oxygen consumption. The data suggest that an increase in metabolic rate and oxygen consumption, induced by the introduction of a high caloric diet, has a protective effect against tumor growth by increasing the activity levels of the tumor suppressor p38 and decreasing the activity of the antiapoptoic protein Bcl-2, as well as by reducing hypoxia-induced tumor vascularization.
... A number of previous studies have examined the effects of overfeeding on EE. Most of these studies have imposed hypercaloric diets for periods of time that do not routinely occur with normal living (29)(30)(31). These studies demonstrate that there is a good deal of heterogeneity in the degree of weight gain following overfeeding suggesting genetic variation in the adaptive responses to overfeeding that either predispose to or protect from weight gain (9,31). ...
Despite living in an environment that promotes weight gain in many individuals, some individuals maintain a thin phenotype while self-reporting expending little or no effort to control their weight. When compared to obesity prone (OP) individuals, we wondered if obesity resistant (OR) individuals would have higher levels of spontaneous physical activity (SPA) or respond to short-term overfeeding by increasing their level of SPA in a manner that could potentially limit future weight gain. SPA was measured in fifty-five subjects (23 OP, 32 OR) using a novel physical activity monitoring system (PAMS) that measured body position and movement while subjects were awake for 6 days, either in a controlled eucaloric condition or during 3 days of overfeeding (1.4 x basal energy) and for the subsequent 3 days (ad libitum recovery period). Pedometers were also used before and during use of the PAMS to provide an independent measure of SPA. SPA was quantified by the PAMS as fraction of recording time spent lying, sitting or in an upright posture. Accelerometry, measured while subjects were in an upright posture, was used to categorize time spent in different levels of movement (standing, walking slowly, quickly, etc.). There were no differences in SPA between groups when examined across all study periods (p>0.05). However, 3 days following overfeeding, OP subjects significantly decreased the amount of time they spent walking (-2.0% of time, p=0.03), while OR subjects maintained their walking (+0.2%, p>0.05). The principle findings of this study are that increased levels of SPA either during eucaloric feeding or following short term overfeeding likely do not significantly contribute to obesity resistance while a decrease in SPA following overfeeding may contribute to future weight gain in individuals prone to obesity.
... However, heightened metabolism might have also been induced, in part, by the increased food intake on the part of the CHip-lesioned rats. Several studies have shown that metabolism increases, perhaps as a counterregulatory response, when animals are forced to consume calories in excess of their metabolic needs ( (Balkan et al., 1993;Harris et al., 2006;Shibata and Bukowiecki, 1987;Weyer et al., 2001). It may be that increased metabolism is an effect of excess caloric intake that was difficult for rats with CHip lesions to control. ...
The effects of selective ibotenate lesions of the complete hippocampus (CHip), the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male rats were assessed on several measures related to energy regulation (i.e., body weight gain, food intake, body adiposity, metabolic activity, general behavioral activity, conditioned appetitive responding). The testing conditions were designed to minimize the nonspecific debilitating effects of these surgeries on intake and body weight. Rats with CHip and VP lesions exhibited significantly greater weight gain and food intake compared with controls. Furthermore, CHip-lesioned rats, but not rats with VP lesions, showed elevated metabolic activity, general activity in the dark phase of the light-dark cycle, and greater conditioned appetitive behavior, compared with control rats without these brain lesions. In contrast, rats with mPFC lesions were not different from controls on any of these measures. These results indicate that hippocampal damage interferes with energy and body weight regulation, perhaps by disrupting higher-order learning and memory processes that contribute to the control of appetitive and consummatory behavior.
Many dieters experience years of yo-yo weight fluctuation. Typically, the yo-yo effect is described as being able to lose weight on a diet but invariably, the lost weight is regained in the long-term. The weight set-point theory explains these dietary failures by hypothesizing that each individual has a weight setting which is determined by a combination of genetic, epigenetic, and environmental factors. When an individual’s weight diverges from the set-point, a biological homeostatic response occurs. Changes in appetite, satiety, and basal metabolic rate occur to defend the set-point weight. Powerful fluctuations occur in the expenditure of basal metabolic energy via the autonomic nervous system.
Objective:
Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.
Research design and methods:
We overfed 38 overweight subjects (age 48 ± 2, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.
Results:
Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.
Conclusions:
Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.
Purpose:
Mechanisms in energy balance (EB) regulation may include compensatory changes in energy intake (EI) and metabolic adaption (MA), but information is unavailable in athletes who often change EB components. We aim to investigate EB regulation compensatory mechanisms over one athletic season.
Methods:
Fifty-seven athletes (39 males/18 females; handball, volleyball, basketball, triathlon, and swimming) were evaluated from the beginning to the competitive phase of the season. Resting and total energy expenditure (REE and TEE, respectively) were assessed by indirect calorimetry and doubly labeled water, respectively, and physical activity energy expenditure was determined as TEE - 0.1(TEE) - REE. Fat mass (FM) and fat-free mass (FFM) were evaluated by dual-energy x-ray absorptiometry and changed body energy stores was determined by 1.0(ΔFFM/Δtime) + 9.5(ΔFM/Δtime). EI was derived as TEE + EB. REE was predicted from baseline FFM, FM, sex, and sports. %MA was calculated as 100(measured REE/predicted REE-1) and MA (kcal) as %MA/100 multiplied by baseline measured REE. Average EI minus average physical activity energy expenditure was computed as a proxy of average energy availability, assuming that a constant nonexercise EE occurred over the season.
Results:
Body mass increased by 0.8 ± 2.5 kg (P < 0.05), but a large individual variability was found ranging from -6.1 to 5.2 kg. The TEE raise (16.8% ± 11.7%) was compensated by an increase EI change (16.3% ± 12.0%) for the whole group (P < 0.05). MA was found in triathletes, sparing 128 ± 168 kcal·d, and basketball players, dissipating 168 ± 205 kcal·d (P < 0.05). MA was associated (P < 0.05) with EB and energy availability (r = 0.356 and r = 0.0644, respectively).
Conclusion:
TEE increased over the season without relevant mean changes in weight, suggesting that EI compensation likely occurred. The thrifty or spendthrift phenotypes observed among sports and the demanding workloads these athletes are exposed to highlight the need for sport-specific energy requirements.
A low level of physical activity, typical of Western society, is deemed conducive to weight gain, while an increase in physical activity tends to promote weight loss, suggesting an imperfect coupling between energy expenditure and intake. Conversely, individuals with high levels of habitual activity tend to be in energy balance over the long-term suggesting that intake is adjusted to match expenditure. There are four interactions to consider between energy intake and expenditure in the development and treatment of obesity. Does exercise drive energy intake upwards and undermine its contribution to weight management? Does sedentariness alter levels of energy intake or subsequent energy expenditure? Do high levels of energy intake alter physical activity or exercise? And does dieting elevate or decrease energy expenditure? Cross talk between elevated energy expenditure and intake is initially too weak and takes too long to activate, to seriously threaten dietary approaches to weight management. It appears that substantial fat loss is possible before intake begins to track a sustained elevation in expenditure. There is little evidence that sedentariness produces compensatory reductions in energy intake. This lack of cross talk between altered expenditure and intake tends to promote a positive energy balance. Sizeable, compensatory changes in nonexercise activity in response to overfeeding are feasible, but have yet to be clearly demonstrated. There is more evidence that energy intake restriction does lower physical activity levels (PALs) – at least when it is more severe and for longer than is recommended for normal dieting and weight loss. A higher level or duration of physical activity is needed to prevent weight regain after dieting than is needed to prevent weight gain in the first place. Even more is needed to achieve weight loss through exercise alone. Individuals who are regularly physically active tend to be leaner and have a lower body weight than those who are sedentary. Taking up regular exercise results in weight loss or maintenance, while stopping results in weight gain. However, individuals vary in their ability to adjust or regulate the various components of energy balance, and therefore in their resistance to lose or gain weight in response to increases or decreases in energy expenditure respectively.
According to Lavoisier, 'Life is combustion'. But to what extent humans adapt to changes in food intake through adaptive thermogenesis - by turning down the rate of heat production during energy deficit (so as to conserve energy) or turning it up during overnutrition (so as to dissipate excess calories) - has been one of the most controversial issues in nutritional sciences over the past 100 years. The debate nowadays is not whether adaptive thermogenesis exists or not, but rather about its quantitative importance in weight homoeostasis and its clinical relevance to the pathogenesis and management of obesity. Such uncertainties are likely to persist in the foreseeable future primarily because of limitations to unobtrusively measure changes in energy expenditure and body composition with high enough accuracy and precision, particularly when even small inter-individual variations in thermogenesis can, in dynamic systems and over the long term, be important in the determining weight maintenance in some and obesity and weight regain in others. This paper reviews the considerable body of evidence, albeit fragmentary, suggesting the existence of quantitatively important adaptive thermogenesis in several compartments of energy expenditure in response to altered food intake. It then discusses the various limitations that lead to over- or underestimations in its assessment, including definitional and semantics, technical and methodological, analytical and statistical. While the role of adaptive thermogenesis in human weight regulation is likely to remain more a concept than a strictly 'quantifiable' entity in the foreseeable future, the evolution of this concept continues to fuel exciting hypothesis-driven mechanistic research which contributes to advance knowledge in human metabolism and which is bound to result in improved strategies for the management of a healthy body weight.
The role of diet composition in response to overeating and energy dissipation in humans is unclear.
To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition.
A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007.
After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884-1022 kcal/d).
Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8.
Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88-4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84-7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23-7.79 kg) (P = .002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102-218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165-289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11-3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37-3.98 kg]) increased significantly with the normal and high protein diets.
Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage.
clinicaltrials.gov Identifier: NCT00565149.
In adults, adjustments in resting energy expenditure (REE) are used to defend energy balance against disturbance caused by over-and under-nutrition, and may be linked to changes in insulin resistance and leptin. Little is known of these associations in children. Our aim was to test the hypothesis that long-term weight gain in children is met with adaptive changes in resting energy expenditure, mediated by insulin resistance and/or leptin.
REE by indirect calorimetry, anthropometry, body composition by DEXA, insulin resistance (HOMA-IR) and serum leptin were measured annually in 232 children from the age of 7-10 y.
REE rose from 7 to 10 y, and the rise exceeded that predicted by the concurrent rise in fat and fat-free mass by 184 kcal/day in the boys and by 160 kcal/day in the girls. However, there were no significant relationships in either gender between this 'excess' rise in REE and change in body composition (r < or = 0.08, p > or = 0.42). The rise in both boys and girls was associated with, but not explained by, a rise in insulin resistance (p < or = 0.002). There was no association with serum leptin (p > or = 0.32).
The data do not support the hypothesis of adaptive changes in REE in pre-pubertal children, and insulin resistance explains very little of the pre-pubertal rise in REE. The rise in REE beyond that explained by changes in body composition may reflect an increase in energy requirements prior to puberty.
Context The prevalence of obesity and overweight increased in the United States
between 1978 and 1991. More recent reports have suggested continued increases
but are based on self-reported data.Objective To examine trends and prevalences of overweight (body mass index [BMI]
≥25) and obesity (BMI ≥30), using measured height and weight data.Design, Setting, and Participants Survey of 4115 adult men and women conducted in 1999 and 2000 as part
of the National Health and Nutrition Examination Survey (NHANES), a nationally
representative sample of the US population.Main Outcome Measure Age-adjusted prevalence of overweight, obesity, and extreme obesity
compared with prior surveys, and sex-, age-, and race/ethnicity–specific
estimates.Results The age-adjusted prevalence of obesity was 30.5% in 1999-2000 compared
with 22.9% in NHANES III (1988-1994; P<.001).
The prevalence of overweight also increased during this period from 55.9%
to 64.5% (P<.001). Extreme obesity (BMI ≥40)
also increased significantly in the population, from 2.9% to 4.7% (P = .002). Although not all changes were statistically significant,
increases occurred for both men and women in all age groups and for non-Hispanic
whites, non-Hispanic blacks, and Mexican Americans. Racial/ethnic groups did
not differ significantly in the prevalence of obesity or overweight for men.
Among women, obesity and overweight prevalences were highest among non-Hispanic
black women. More than half of non-Hispanic black women aged 40 years or older
were obese and more than 80% were overweight.Conclusions The increases in the prevalences of obesity and overweight previously
observed continued in 1999-2000. The potential health benefits from reduction
in overweight and obesity are of considerable public health importance.
1. Studies have claimed that an enhancement of the thermic effect of a meal (TEM) is an important adaptive mechanism to account for energy wastage during over-feeding.
2. Eight healthy normal-weight young men were studied during 1 week on a weight-maintenance diet and again during 1 week when they were over-fed by 50% with fat. During each experimental week, the subject occupied a whole-body indirect calorimeter at 26° for two separate periods of 36 h. The periods differed in the amount of exercise they contained. The thermic responses to the identical meals were measured during rest on one occasion and during exercise on a bicycle ergometer on the other.
3. On the maintenance diet the absolute TEM (kJ/min) was 1.51 (SD 0.42) at rest and 1.31 (SD 0.75) during exercise (no significant difference). The equivalent values (kJ/min) on the over-feeding diet were 2.2 (SD 0.48) and 1.97 (SD 0.64) (no significant difference).
4. The absence of a significant interaction between TEM and exercise was also demonstrated by the fact that the effect of over-feeding on total 24 h energy expenditure was unaffected by the subject's level of physical activity while in the calorimeter.
5. In conclusion, the present study has provided no evidence to support the hypothesis that TEM is enhanced during exercise.
This report deals with the association between the constituents of lean body mass (LBM) and resting metabolic rate (RMR) before and after a 100-d overfeeding period. Computed-tomography (CT) scan of 22 young adult males at nine different body levels were used to estimate adipose tissue mass (ATMCT), LBMCT, skeletal-muscle mass (SMMCT), and non-muscular LBMCT (NM-LBMCT). Before overfeeding, all body constituents, except ATMCT, were significantly correlated with RMR. Only body mass changes were significantly correlated with RMR changes. Comparison of these results with those of several studies in the literature reveals that the relationship between RMR and fat-free mass is highly influenced by the size of the SD for the latter variable. In stepwise-multiple-regression analysis, only SMMCT could be used to predict RMR. It was concluded that SMMCT and ATMCT, but not NM-LBMCT, increased during overfeeding and that the best correlates of RMR remain LBMCT, SMMCT, and body massType: JOURNAL ARTICLELanguage: Eng
The effect of overfeeding on energy expenditure was investigated in 23 young men subjected to a 353-MJ energy intake surplus over 100 d. The major part of this excess (222 MJ) was stored as body energy. The increase in energy cost of weight maintenance amounted to 52 MJ and was proportional to body weight gain. When it was added to the obligatory cost of fat and fat-free mass gains, the overall increase in energy expenditure amounted to a mean of 100 MJ. Four months after overfeeding, subjects had lost 82%, 74%, and 100% of the overfeeding gain in body weight, fat mass, and fat-free mass, respectively. We conclude that 1) in response to overfeeding, two-thirds of the excess energy intake is stored as body energy; 2) overfeeding induces an increase in energy cost of weight maintenance proportional to body weight gain, and 3) preoverfeeding energy balance tends to be restored when nonobese individuals return to their normal daily-life habits.
Possible adaptive mechanisms that may defend against weight gain during periods of excessive energy intake were investigated by overfeeding six lean and three overweight young men by 50% above baseline requirements with a mixed diet for 42 d [6.2 +/- 1.9 MJ/d (mean +/- SD), or a total of 265 +/- 45 MJ]. Mean weight gain was 7.6 +/- 1.6 kg (58 +/- 18% fat). The energy cost of tissue deposition (28.7 +/- 4.4 MJ/kg) matched the theoretical cost (26.0 MJ/kg). Basal metabolic rate (BMR) increased by 0.9 +/- 0.4 MJ/d and daily energy expenditure assessed by whole-body calorimetry (CAL EE) increased by 1.8 +/- 0.5 MJ/d. Total free-living energy expenditure (TEE) measured by doubly labeled water increased by 1.4 +/- 2.0 MJ/d. Activity and thermogenesis (computed as CAL EE--BMR and TEE--BMR) increased by only 0.9 +/- 0.4 and 0.9 +/- 2.1 MJ/d, respectively. All outcomes were consistent with theoretical changes due to the increased fat-free mass, body weight, and energy intake. There was no evidence of any active energy-dissipating mechanisms.
Respiratory exchange was measured during 14 consecutive hours in six lean and six obese individuals after ingestion of 500 g of dextrin maltose to investigate and compare their capacity for net de novo lipogenesis. After ingestion of the carbohydrate load, metabolic rates rose similarly in both groups but fell earlier and more rapidly in the obese. RQs also rose rapidly and remained in the range of 0.95 to 1.00 for approximately 8 h in both groups. During this time, RQ exceeded 1.00 for only short periods of time with the result that 4 +/- 1 g and 5 +/- 3 g (NS) of fat were synthesized via de novo lipogenesis in excess of concomitant fat oxidation in the lean and obese subjects, respectively. Results demonstrate that net de novo lipid synthesis from an unusually large carbohydrate load is not greater in obese than in lean individuals.
After 13 days of weight maintenance diet (13,720 +/- 620 kJ/day, 40% fat, 15% protein, and 45% carbohydrate), five young men (71.3 +/- 7.1 kg, 181 +/- 8 cm; means +/- SD) were overfed for 9 days at 1.6 times their maintenance requirements (i.e., +8,010 kJ/day). Twenty-four-hour energy expenditure (24-h EE) and basal metabolic rate (BMR) were measured on three occasions, once after 10 days on the weight-maintenance diet and after 2 and 9 days of overfeeding. Physical activity was monitored throughout the study, body composition was measured by underwater weighing, and nitrogen balance was assessed for 3 days during the two experimental periods. Overfeeding caused an increase in body weight averaging 3.2 kg of which 56% was fat as measured by underwater weighing. After 9 days of overfeeding, BMR increased by 622 kJ/day, which could explain one-third of the increase in 24-h EE (2,038 kJ/day); the remainder was due to the thermic effect of food (which increased in proportion with excess energy intake) and the increased cost of physical activity, related to body weight gain. This study shows that approximately one-quarter of the excess energy intake was dissipated through an increase in EE, with 75% being stored in the body. Under our experimental conditions of mixed overfeeding in which body composition measurements were combined with those of energy balance, it was possible to account for all of the energy ingested in excess of maintenance requirements.
1. The metabolic effects of increasing or decreasing the usual energy intake for only 1 d were assessed in eight adult volunteers. Each subject lived for 28 h in a whole-body calorimeter at 26° on three separate occasions of high, medium or low energy intake. Intakes (mean±SEM) of 13830 ± 475 (high), 8400 ± 510 (medium) and 3700 ± 359 (low) kJ/24 h were eaten in three meals of identical nutrient composition.
2. Energy expenditure was measured continuously by two methods: direct calorimetry, as total heat loss partitioned into its evaporative and sensible components; and indirect calorimetry, as heat production calculated from oxygen consumption and carbon dioxide production. For the twenty-four sessions there was a mean difference of only 1.2 ± 0.14 (SEM)% between the two estimates of 24 h energy expenditure, with heat loss being less than heat production. Since experimental error was involved in both estimates it would be wrong to ascribe greater accuracy to either one of the measures of energy expenditure.
3. Despite the wide variation in the metabolic responses of the subjects to over-eating and under-eating, in comparison with the medium intake the 24 h heat production increased significantly by 10% on the high intake and decreased by 6% on the low intake. Mean (± SEM) values for 24 h heat production were 8770 ± 288, 7896 ± 297 and 7495 ± 253 kJ on the high, medium and low intakes respectively. The effects of over-eating were greatest at night and the resting metabolic rate remained elevated by 12% 14 h after the last meal. By contrast, during under-eating the metabolic rate at night decreased by only 1%.
4. Evaporative heat loss accounted for an average of 25% of the total heat loss at each level of intake. Changes in evaporative heat loss were +14% on the high intake and −10% on the low intake. Sensible heat loss altered by +9% and −5% on the high and low intakes respectively.
5. It is concluded that ( a ) the effects on 24 h energy expenditure of over-feeding for only 1 d do not differ markedly from those estimated by some other workers after several weeks of increasing the energy intake; ( b ) the resting metabolic rate, measured at least 14 h after the last meal, can be affected by the previous day's energy intake; ( c ) the zone of ambient temperature within which metabolism is minimal is probably altered by the level of energy intake.
No current treatment for obesity reliably sustains weight loss, perhaps because compensatory metabolic processes resist the maintenance of the altered body weight. We examined the effects of experimental perturbations of body weight on energy expenditure to determine whether they lead to metabolic changes and whether obese subjects and those who have never been obese respond similarly.
We repeatedly measured 24-hour total energy expenditure, resting and nonresting energy expenditure, and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding.
Maintenance of a body weight at a level 10 percent or more below the initial weight was associated with a mean (+/- SD) reduction in total energy expenditure of 6 +/- 3 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 5 kcal per kilogram per day in the obese subjects (P < 0.001). Resting energy expenditure and nonresting energy expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in both groups of subjects. Maintenance of body weight at a level 10 percent above the usual weight was associated with an increase in total energy expenditure of 9 +/- 7 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 4 kcal per kilogram per day in the obese subjects (P < 0.001). The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day, respectively, after weight gain. These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects.
Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure, which oppose the maintenance of a body weight that is different from the usual weight. These compensatory changes may account for the poor long-term efficacy of treatments for obesity.
To identify and quantify the major external (nongenetic) factors that contribute to death in the United States.
Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and complications of vital statistics and surveillance data were also obtained.
Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity.
Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates.
The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400,000 deaths), diet and activity patterns (300,000), alcohol (100,000), microbial agents (90,000), toxic agents (60,000), firearms (35,000), sexual behavior (30,000), motor vehicles (25,000), and illicit use of drugs (20,000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations.
Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities.
Humans show considerable interindividual variation in susceptibility to weight gain in response to overeating. The physiological
basis of this variation was investigated by measuring changes in energy storage and expenditure in 16 nonobese volunteers
who were fed 1000 kilocalories per day in excess of weight-maintenance requirements for 8 weeks. Two-thirds of the increases
in total daily energy expenditure was due to increased nonexercise activity thermogenesis (NEAT), which is associated with
fidgeting, maintenance of posture, and other physical activities of daily life. Changes in NEAT accounted for the 10-fold
differences in fat storage that occurred and directly predicted resistance to fat gain with overfeeding (correlation coefficient
= 0.77, probability < 0.001). These results suggest that as humans overeat, activation of NEAT dissipates excess energy to
preserve leanness and that failure to activate NEAT may result in ready fat gain.
Obesity is a major health problem in the United States, but the number of obesity-attributable deaths has not been rigorously estimated.
To estimate the number of deaths, annually, attributable to obesity among US adults.
Data from 5 prospective cohort studies (the Alameda Community Health Study, the Framingham Heart Study, the Tecumseh Community Health Study, the American Cancer Society Cancer Prevention Study I, and the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study) and 1 published study (the Nurses' Health Study) in conjunction with 1991 national statistics on body mass index distributions, population size, and overall deaths.
Adults, 18 years or older in 1991, classified by body mass index (kg/m2) as overweight (25-30), obese (30-35), and severely obese (>35).
Relative hazard ratio (HR) of death for obese or overweight persons.
The estimated number of annual deaths attributable to obesity varied with the cohort used to calculate the HRs, but findings were consistent overall. More than 80% of the estimated obesity-attributable deaths occurred among individuals with a body mass index of more than 30 kg/m2. When HRs were estimated for all eligible subjects from all 6 studies, the mean estimate of deaths attributable to obesity in the United States was 280184 (range, 236111-341153). Hazard ratios also were calculated from data for nonsmokers or never-smokers only. When these HRs were applied to the entire population (assuming the HR applied to all individuals), the mean estimate for obesity-attributable death was 324 940 (range, 262541-383410).
The estimated number of annual deaths attributable to obesity among US adults is approximately 280000 based on HRs from all subjects and 325000 based on HRs from only nonsmokers and never-smokers.
Sixteen young adult men and women were fed, for periods of 4–8 weeks, diets containing either about 2.8 or 15% of protein calories, and providing an excess of about 1,400 kcal/day above their normal intake. Measurements were made of body weight, activity, urinary output of nitrogen and creatinine, digestibility of the food, basal metabolic rate, total body potassium, subcutaneous fat, and total body water.
The mean weight gain of the low-protein groups was 1.1 kg compared with a theoretical figure of 5.0 kg if the excess calories are calculated as being converted to adipose tissue containing 66% fat; for the high-protein groups the mean weight gain was 3.7 kg compared with a theoretical figure of 5.4 kg. Since none of the indices of body composition showed any real change during the experimental period, and since activity was both low and unchanged, it is clear that the excess caloric intake of the subjects was disposed of by an increased heat production. This view is supported by the measurement of oxygen consumption reported in our second paper and has implications in the etiology of obesity.
In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 ± 5 g) than in the mixed (300 ± 13 g) or high-CHO diet (331 ± 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 ± 6 g) than in the other two groups (197 ± 11 and 170 ± 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 ± 0.5, 3.4 ± 0.6, and 9 ± 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 ± 0.5% on the high-fat, 6.5 ± 0.4% on the mixed diet, and 8.6 ± 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO lead (r = 0.82) and between net lipogenesis and in the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.
After 13 days of weight maintenance diet (13,720 ± 620 kJ/day, 40% fat, 15% protein, and 45% carbohydrate), five young men (71.3 ± 7.1 kg, 181 ± 8 cm; means ± SD) were overfed for 9 days at 1.6 times their maintenance requirements (i.e., +8,010 kJ/day). Twenty-four-hour energy expenditure (24-h EE) and basal metabolic rate (BMR) were measured on three occasions, once after 10 days on the weight-maintenance diet and after 2 and 9 days of overfeeding. Physical activity was monitored throughout the study, body composition was measured by underwater weighing, and nitrogen balance was assessed for 3 days during the two experimental periods. Overfeeding caused an increase in body weight averaging 3.2 kg of which 56% was fat as measured by underwater weighing. After 9 days of overfeeding, BMR increased by 622 kJ/day, which could explain one-third of the increase in 24-h EE (2,038 kJ/day); the remainder was due to the thermic effect of food (which increased in proportion with excess energy intake) and the increased cost of physical activity, related to body weight gain. This study shows that approximately one-quarter of the excess energy intake was dissipated through an increase in EE, with 75% being stored in the body. Under our experimental conditions of mixed overfeeding in which body composition measurements were combined with those of energy balance, it was possible to account for all of the energy ingested in excess of maintenance requirements.
Context Excess body weight is positively associated with sleep-disordered breathing
(SDB), a prevalent condition in the US general population. No large study
has been conducted of the longitudinal association between SDB and change
in weight.Objective To measure the independent longitudinal association between weight change
and change in SDB severity.Design Population-based, prospective cohort study conducted from July 1989
to January 2000.Setting and Participants Six hundred ninety randomly selected employed Wisconsin residents (mean
age at baseline, 46 years; 56% male) who were evaluated twice at 4-year intervals
for SDB.Main Outcome Measures Percentage change in the apnea-hypopnea index (AHI; apnea events + hypopnea
events per hour of sleep) and odds of developing moderate-to-severe SDB (defined
by an AHI ≥15 events per hour of sleep), with respect to change in weight.Results Relative to stable weight, a 10% weight gain predicted an approximate
32% (95% confidence interval [CI], 20%-45%) increase in the AHI. A 10% weight
loss predicted a 26% (95% CI, 18%-34%) decrease in the AHI. A 10% increase
in weight predicted a 6-fold (95% CI, 2.2-17.0) increase in the odds of developing
moderate-to-severe SDB.Conclusions Our data indicate that clinical and public health programs that result
in even modest weight control are likely to be effective in managing SDB and
reducing new occurrence of SDB.
Objective.
—To identify and quantify the major external (nongenetic) factors that contribute to death in the United States.Data Sources.
—Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and compilations of vital statistics and surveillance data were also obtained.Study Selection.
—Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity.Data Extraction.
—Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates.Data Synthesis.
—The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400000 deaths), diet and activity patterns (300 000), alcohol (100 000), microbial agents (90 000), toxic agents (60 000), firearms (35 000), sexual behavior (30 000), motor vehicles (25 000), and illicit use of drugs (20 000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations.Conclusions.
—Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities.(JAMA. 1993;270:2207-2212)
Obesity has become pandemic in the United States. Currently, 2 in 3
US adults are classified as overweight or obese, compared with fewer than
1 in 4 in the early 1960s.1,2 Although
still viewed more as a cosmetic rather than a health problem by the general
public, excess weight is a major risk factor for premature mortality, cardiovascular
disease, type 2 diabetes mellitus, osteoarthritis, certain cancers, and other
medical conditions.3 Obesity accounts for more
than 280 000 deaths annually in the United States and will soon overtake
smoking as the primary preventable cause of death if current trends continue.4 Indeed, obesity is already associated with greater
morbidity and poorer health-related quality of life than smoking, problem
drinking, or poverty.5 Despite this, excess
weight has not received the same attention from clinicians and policymakers
as have other threats to health such as tobacco use, hypertension, or hypercholesterolemia.
Given these circumstances, it is not surprising that obesity rates continue
to climb, even as significant reductions in other risk factors have been achieved.6
A diabetes epidemic emerged during the 20th century and continues unchecked into the 21st century. It has already taken an extraordinary toll on the U.S. population through its acute and chronic complications, disability, and premature death. Trend data suggest that the burden will continue to increase. Efforts to prevent or delay the complications of diabetes or, better yet, to prevent or delay the development of diabetes itself are urgently needed.
Waist circumference has been proposed as a measure of obesity or as an adjunct to other anthropometric measures to determine obesity. Our objective was to examine temporal trends in waist circumference among adults in the U.S.
We used data from 15,454 participants >/=20 years old in National Health and Nutrition Examination Survey (NHANES) III (1988 to 1994) and 4024 participants >/=20 years old from National Health and Nutrition Examination Survey 1999 to 2000.
The unadjusted waist circumference increased from 95.3 (age-adjusted, 96.0 cm) to 98.6 (age-adjusted, 98.9 cm) cm among men and from 88.7 (age-adjusted 88.9 cm) to 92.2 (age-adjusted 92.1 cm) cm among women. The percentiles from the two surveys suggest that much of the waist circumference distribution has shifted. Statistically significant increases occurred among all age groups and racial or ethnic groups except men 30 to 59 years old, women 40 to 59 and >/=70 years old, and women who were Mexican American or of "other" race or ethnicity.
These results demonstrate the rapid increase in obesity, especially abdominal obesity, among U.S. adults. Unless measures are taken to slow the increase in or reverse the course of the obesity epidemic, the burden of obesity-associated morbidity and mortality in the U.S. can be expected to increase substantially in future years.
Ten slightly obese middle-aged men were instructed to increase their energy intake 25% during a period of 1 week, which was preceded by a control period of seven days. Body weight increased by 0.67 kg (SD 0.60) indicating good compliance with the regimen. Transmembrane sodium fluxes were determined with the use of 22Na. The pre-diet erythrocyte sodium content was 9.7 mmol/L (SD 0.8) decreasing to 8.9 mmol/L (SD 1.1) (P < 0.05) during overfeeding. The Na-efflux rate constant increased from 0.40 h−1 to 0.54 h−1 (P < 0.05). Urinary excretion of catecholamines and concentrations of catecholamines and insulin in plasma and of thyroxine, triiodothyronine, and reverse T3 in serum did not change. Thus, overfeeding seems to enhance the total Na efflux in erythrocytes from slightly obese men. There were no measurable changes in thyroid hormone or catecholamine levels leaving the regulatory mechanisms unexplained.
Diet-induced alterations in thyroid hormone concentrations have been found in studies of long-term (7 mo) overfeeding in man (the Vermont Study). In these studies of weight gain in normal weight volunteers, increased calories were required to maintain weight after gain over and above that predicted from their increased size. This was associated with increased concentrations of triiodothyronine (T3). No change in the caloric requirement to maintain weight or concentrations of T3 was found after long-term (3 mo) fat overfeeding. In studies of short-term overfeeding (3 wk) the serum concentrations of T3 and its metabolic clearance were increased, resulting in a marked increase in the production rate of T3 irrespective of the composition of the diet overfed (carbohydrate 29.6 +/- 2.1 to 54.0 +/- 3.3, fat 28.2 +/- 3.7 to 49.1 +/- 3.4, and protein 31.2 +/- 2.1 to 53.2 +/- 3.7 microgram/d per 70 kg). Thyroxine production was unaltered by overfeeding (93.7 +/- 6.5 vs. 89.2 +/- 4.9 microgram/d per 70 kg). It is still speculative whether these dietary-induced alterations in thyroid hormone metabolism are responsible for the simultaneously increased expenditure of energy in these subjects and therefore might represent an important physiological adaptation in times of caloric affluence. During the weight-maintenance phases of the long-term overfeeding studies, concentrations of T3 were increased when carbohydrate was isocalorically substituted for fat in the diet. In short-term studies the peripheral concentrations of T3 and reverse T3 found during fasting were mimicked in direction, if not in degree, with equal or hypocaloric diets restricted in carbohydrate were fed. It is apparent from these studies that the caloric content as well as the composition of the diet, specifically, the carbohydrate content, can be important factors in regulating the peripheral metabolism of thyroid hormones.
Dietary thermogenesis was studied under carefully controlled dietary and physical activity plans. Eight females, four normal and four overweight, were kept in a metabolic ward and 02 consumption was measured during three periods. The first (5 days) served as a base- line control, in which the subjects ate ad libitum and retained their usual weight. In the second period (5 days), each subject ate a daily excess averaging about 2,300 kcal superimposed on her normal daily intake in the first period. The subjects were then released and dieted at home. After each subject had lost between 2 and 5 kg., she was called for a third period of 2 days during which she ate the same daily excess as in two matching days in the second period. 02 consumption was measured three times daily: at rest after arising in the morning, and during two daily exercise periods, one before breakfast, and the other after breakfast. Leisure time activity was controlled throughout the experiment. It was found that: 1) There was no increase in 02 consumption during the two overfeeding periods as compared to control, either at rest or during the exercise periods. 2) There was no difference between the normal and overweight subjects in their responses to overfeeding. 3) There was no increased efficiency in energy utilization during overfeeding which followed a state of energy deficit, as compared to overfeeding which followed a state of energy balance. It is suggested that an increased dietary thermogenesis is not a factor in the regulation of energy balance during periods of overeating hasting several days only. Am. J. Clin. Nut,'. 30: 1026-1035, 1977.
This study compares the continuous response of six underweight (UW) (body mass index [BMI] < 18 kg/m2) and six normal-weight (NW) (20 < BMI < 25) men of similar age to a modest but sustained level of underfeeding and overfeeding. Habitual energy intake over 4 wk, body composition, and basal metabolic rate (BMR) were measured under metabolic-ward conditions. NW subjects were heavier by 9 kg and had 5% more body fat than UW subjects. The average BMR of UW subjects was 7.5% lower than NW subjects in absolute terms and also per kilogram fat-free mass per day but was higher by 8% when expressed per kilogram body weight per day. Three NW and three UW subjects were given a diet with 10% less energy than their habitual intake for 4 wk. They were brought back to the normal level of feeding for another 4 wk. Finally, they were overfed by 10% for 4 wk. This sequence was reversed in the remaining six subjects. Changes in body weight, BMR, and energy balance were assessed. UW subjects showed a quick and vigorous reduction in BMR (13.4%) during the 1st wk of underfeeding compared with NW subjects (8.1%). In the later weeks, the reduction was 8% in UW and 7% in NW subjects. Furthermore, UW subjects showed a tendency to resist a decrease in body weight (mean loss 180 g), unlike NW subjects (mean loss 730 g). With overfeeding, the mean increase in BMR for UW was higher (7.4%) than for NW (5.3%) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
We investigated the mechanisms of body weight regulation in young men of normal body weight leading unrestricted lives. Changes in total and resting energy expenditure, body composition, and subsequent voluntary nutrient intakes in response to overeating by 4,230 +/- 115 (SE) kJ/day (1,011 +/- 27 kcal/day) for 21 days were measured in seven subjects consuming a typical diet. On average, 85-90% of the excess energy intake was deposited (with 87% of this amount in fat and 13% in protein on average). There was no detectable difference between individuals in susceptibility to energy deposition. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (mean +/- SE, 628 +/- 197 kJ/day, P less than 0.01), but at least some of this amount was obligatory expenditure associated with nutrient assimilation. No significant increase in energy expenditure for physical activity or thermoregulation resulted from overfeeding. Thus energy expenditure did not substantially adapt to increased energy intake. However, significant decreases in voluntary energy intake (1,991 +/- 824 kJ/day, P less than 0.05) and fat intake (48 +/- 11 g/day, P less than 0.01) followed overeating, indicating that adaptive changes in nutrient intakes can contribute significantly to body weight regulation after overeating.
Overfeeding increases the thermogenic response of norepinephrine (NE) in normal but not in certain genetically obese rodents. It has been suggested that human obesity may be associated with a similar thermogenic defect. To determine whether there are differences in the thermogenic sensitivity to NE in human obesity, energy expenditure in response to graded infusions of NE (0.05, 0.10, 0.15, 0.20 micrograms/min/kg fat-free mass) was measured in six lean and six obese subjects (9.5 +/- 1.8 v 36.3 +/- 3.8% body fat P less than 0.005). Resting metabolic rate (RMR), thermogenic response to NE, and thermogenic response to exercise were measured during weight maintenance and during the third week of feeding 1000 extra Kcal/d in the lean and obese subjects. These components of energy expenditure were also measured in the obese subjects during the third week of a 589 Kcal/d diet. Resting metabolic rate increased during overfeeding in lean (6.6%, P less than 0.05) but not in the obese subjects (2.7%, P = NS) and fell during underfeeding in the obese (-9.1%, P less than 0.02). There was a logarithmic increment above baseline in VO2 v plasma NE concentration during the NE infusions (r = 0.75, P less than 0.005) in lean subjects which was unaltered by overfeeding. The obese exhibited equivalent VO2 responses to NE to that measured in the lean. Supine plasma NE concentrations were lower but metabolic clearance rates (MCR) of NE were similar in the obese compared to lean subjects during both weight maintenance and overfeeding. Overfeeding minimally increased plasma concentration but not MCR of NE in both groups. The thermogenic response to exercise was similar in the lean and obese subjects and was unaltered by overfeeding or underfeeding. The increments in plasma glycerol and free fatty acid in response to the NE infusions were proportional to the total fat mass of each individual and were greater in the obese subjects. Overfeeding partially suppressed the lipolytic response to NE in both groups and underfeeding increased the lipolytic response in the obese. There are no differences in thermogenic responses to NE in human obesity to account for excessive fat deposition. Overfeeding does not increase the thermogenetic responses to NE in humans as has been reported in small mammals.
1. Thirteen adult females and two males were overfed a total of 79–159 MJ (1900–38 000 kcal) during a 3-week period at the Clinical Research Center, Rochester. The average energy cost of the weight gain was 28 kJ (6.7 kcal)/g, and about half the gain consisted of lean body mass (LBM) as estimated by ⁴⁰ Kcounting.
2. A survey of the literature disclosed twenty-eight normal males and five females who had been overfed a total of 104–362 MJ (2500–87000 kcal) under controlled conditions: twenty-five of these had assays of body composition, and three had complete nitrogen balances.
3. When these values were combined with those from our subjects (total forty-eight), there was a significant correlation between weight gain and total excess energy consumed ( r 0.77, P < 0.01) and between LBM gain and excess energy ( r 0.49, P < 0.01). Based on means the energy cost was 33.7 kJ (8.05 kcal)/g gain and 43.6% of the gain was LBM; from regression analysis these values were 33.7 kJ (8.05 kcal)/g gain and 38.4% of gain as LBM.
4. Individual variations in the response could not be explained on the basis of sex, initial body-weight or fat content, duration of overfeeding, type of food eaten, amount of daily food consumption or, in a subset of subjects, on smoking behaviour.
5. The average energy cost of the weight gain was close to the theoretical value of 33.8 kJ (8.08 kcal)/g derived from the composition of the tissue gained.
Metabolic responses to 20 days of overeating were examined in five healthy volunteers. Overfeeding caused a variable increase (1-18%) in basal metabolic rate but no change in metabolic rate during light exercise. Postprandial resting metabolic rate was 8-40% higher (mean 18%) during overeating. The increase in oxygen consumption during a norepinephrine infusion was the same before (20 +/- 2%) and after (17 +/- 3%) overfeeding. Overfeeding elevated basal insulin concentrations in all subjects and increased the insulin response to intravenous glucose in four of five subjects. Overfeeding did not significantly alter mean serum T3 concentrations or erythrocyte 86Rb uptake (an index of Na+,K+-ATPase activity). These data do not confirm reports that overfeeding increases metabolic rate more during exercise than during rest. They also suggest that the increase in resting metabolic rate during overfeeding is not caused by increased responsiveness to norepinephrine or increased serum T3 concentrations.
Eight obese and eight lean women were studied in a metabolic unit for up to 4 weeks to assess the thermogenic response to fat overfeeding. An extra 4.3 MJ fat were given to both obese and lean groups for 6 days after a preliminary weight-maintenance diet. The fat overfeeding was repeated following a period of semistarvation. The obese women initially had a higher 4-h expenditure (9.9 +/- 1.1 MJ) than the lean (7.4 +/- 0.6 MJ). Fat overfeeding induced a variable increase in energy output (340 +/- 197 kJ in the obese and 612 +/- 147 kJ in the lean) amounting to 7.8 +/- 4.5 percent of the supplement's energy in the obese and 14.2 +/- 3.4 percent in the lean. The response to the fat supplement during semistarvation remained low in the obese at 3.6 +/- 4.9 percent but fell substantially in the lean (8.1 +/- 3.8 percent). These results suggest that there is a flexibility in the normal thermogenic response to fat in lean subjects but a reduced response in those with familial obesity.
To assess whether thermogenesis or sympathetic nervous system (SNS) function might differ between lean and obese human subjects, studies of thermic and sympathetic responses to standard stimuli were undertaken in Pima Indians, an ethnic group with a high prevalence of obesity. Plasma levels of norepinephrine (NE) and energy expenditure at rest and in response to feeding, exercise, and graded infusions of NE were compared in five lean and five obese Indians during a period of weight maintenance (WM), after 3 weeks of overfeeding (OF) and, in the obese, also after 6 weeks of underfeeding (UF). Basal energy expenditure, when adjusted for fat free mass, was equivalent during WM and increased 3% with OF (P less than 0.01) in both groups. Thermic responses to exercise or a test meal did not differ in lean and obese and did not change with OF, while thermic responses to NE infusion fell during OF to a greater degree in obese than lean (P less than 0.05). A similar pattern (decreased effect in obese with OF) was also noted in the glycemic response to infused NE (P less than 0.05). Although not quantitatively different in lean and obese, the plasma NE concentration appeared to vary more in response to feeding or dietary alteration in the obese than lean, a finding that may reflect lower plasma clearance of NE in the obese. These studies, therefore, raise the possibility that overfeeding in obese Pima Indians may limit the contribution of sympathetically mediated thermogenesis to energy expenditure, though the implications of this for body weight regulation are speculative.
The oxygen consumption of three groups of individuals was determined at two 15-day intervals, using two types of apparatus and a special metabolic room. Nine subjects who
[See table in the PDF file]
received a normal diet served as controls; eight consumed an isoprotein diet that included a 1,500-kcal/day supplement; and 41 obese subjects were restricted to an intake of 220 kcal/day, which consisted of 55 g casein, potassium chloride, vitamins, and water. All experimental diets followed a control period on a normal diet.
Measurements of Vo2were made with the subjects in the basal state and also when they performed physical activities while fasting. The group (B), who overate, showed an increase in energy expenditure of 12 to 29%, whereas group C (those receiving the restricted diet) had a decrease of 12 to 17%.
Our results on oxygen consumption were compatible with each other and with the weight changes experienced by the subjects studied.
The relative Cl- and K+ sensitivity of the basolateral membrane potential of the in vitro Necturus gallbladder epithelium was determined. Tissues were punctured with two conventional glass microelectrodes to simultaneously measure the intracellular voltage (Vcs) and the voltage across the subepithelial connective tissue (Vse). Increasing the serosal K+ concentration from 2.5 to 25 mM caused a rapid monotonic depolarization of Vcs without changes of Vse. Reduction of serosal Cl- concentration (98 to 8 mM) caused a transient change of Vse. Thus the difference between Vcs and Vse more accurately reflected the basolateral membrane voltage (Vc) after Cl- concentration changes. The changes of Vc were small and biphasic in response to the decrease of serosal Cl- concentration. Perfusion of a low-ionic-strength solution in the mucosal chamber decreased the current that normally passes through the epithelium. Consistent with the notion that the basolateral voltage changes are attenuated by parallel pathways, the K+-induced depolarization increased by 80% under these conditions. The changes of Vc in response to Cl- substitutions were not different from those of tissue bathed in control solution. Thus the basolateral membrane voltage is relatively insensitive to changes of serosal Cl- concentration. I conclude that Cl- movement across the basolateral membrane is not attributable to simple electrodiffusion, and Cl- exit from these cells at this membrane must be electroneutral.
The relationship between the degree of obesity and the incidence of cardiovascular disease (CVD) was reexamined in the 5209 men and women of the original Framingham cohort. Recent observations of disease occurrence over 26 years indicate that obesity, measured by Metropolitan Relative Weight, was a significant independent predictor of CVD, particularly among women. Multiple logistic regression analyses showed that Metropolitan Relative Weight, or percentage of desirable weight, on initial examination predicted 26-year incidence of coronary disease (both angina and coronary disease other than angina), coronary death and congestive heart failure in men independent of age, cholesterol, systolic blood pressure, cigarettes, left ventricular hypertrophy and glucose intolerance. Relative weight in women was also positively and independently associated with coronary disease, stroke, congestive failure, and coronary and CVD death. These data further show that weight gain after the young adult years conveyed an increased risk of CVD in both sexes that could not be attributed either to the initial weight or the levels of the risk factors that may have resulted from weight gain. Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.
Daily carbohydrate intake of seven men with normal weight was limited to 220-265 g/d for 6 d and then increased to 620-770 g/d for 20 d, while intake of protein, fat, and sodium remained constant. Carbohydrate overfeeding increased body weight by 4.8%, basal oxygen consumption (VO2) by 7.4%, BMR by 11.5%, and serum triiodothyronine levels by 32%. Overfeeding did not affect the thermic effect of a standard meal. Intravenous propranolol reduced the thermic effect of a meal by 22% during the base-line feeding period, and by 13% during carbohydrate overfeeding, but did not affect preprandial VO2. Overfeeding attenuated the rise in plasma glucose and FFA levels induced by infusion of norepinephrine, but had no effect on the increase in VO2 induced by norepinephrine. Overfeeding did not alter 24-h urinary excretion of vanillylmandelic acid, supine plasma catecholamine levels (pre- and postprandial), blood pressure, or plasma renin activity, but increased peak standing plasma norepinephrine levels by 45% and resting pulse rate by 9%. Even though short-term carbohydrate overfeeding may produce modest stimulation of sympathetic nervous system activity in man, the increase in thermogenesis induced by such overfeeding is neither suppressed by beta adrenergic blockade nor accompanied by an increased sensitivity to the thermogenic effects of norepinephrine. These data do not support an important role for the sympathetic nervous system in mediating the thermogenic response to carbohydrate overfeeding.
Strong support has been gathered for a defect in insulin-glucose-mediated thermogenesis in obese and particularly obese insulin-resistant and/or diabetic subjects compared to lean subjects. This defect appears to be reversible with weight loss and improved insulin sensitivity. The mechanism for this blunted thermogic response is directly related to the decreased glucose storage in the obese and obese diabetic subjects.
The question of the proper size denominator for metabolic indices is addressed. Metabolic rate among different species is proportional to the 3/4 power of body weight, not surface area. Muscle power also varies with the 3/4 power of weight, suggesting that metabolic rate is determined mainly by muscle power. Power-to-weight ratio, specific metabolic rate, and a number of metabolic periods, including heart rate, all vary inversely with the 1/4 power of body weight. Thus the relative times required for physiological and pathological processes in different species may be estimated from the average resting heart rate for the species. There are not many small humans among athletic record holders in events involving acceleration and hill climbing, as would be expected if they had higher power-to-weight ratios. Thus the relationship between size and metabolic rate in different species should not be applied within the single species of humans. Evidence is reviewed showing that basal metabolic rate in humans is determined mainly by lean body mass.
In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.
Eight young men of normal weight were maintained for 1 week on a weight-maintenance diet followed by a 1-week period of over-feeding with extra fat designed to increase energy intake by 50%. Two 36 h calorimetry sessions with low and high physical activities were included in each feeding period. Faecal and urine collections permitted checks on energy malabsorption and nitrogen excretion. Over-feeding led to increases in body-weight, faecal energy and N excretion and in estimated N retention. Faecal energy outputs on the maintenance and over-feeding diets were 5 and 4.4% of the respective gross energy intakes. Energy expenditure on fat over-feeding increased by 5.6% on the low-activity regimen and 6.4% on the high-activity regimen. This amounted, in terms of the extra energy intake, to 9 and 11% on the inactive and active schedules respectively. The increase affected day- and night-time rates of energy expenditure plus the basal metabolic rate. Individuals with a low percentage body fat showed the greatest response to over-feeding. Nutrient-balance studies derived from calorimetry suggested that fat over-feeding led to substantial fat deposition with no evidence of sparing of carbohydrate oxidation. The theoretical cost of depositing dietary fat was exceeded, suggesting that regulatory thermogenic mechanisms may have been stimulated to a small extent.
Both excess weight and hypertension may contribute independently to increased risk of cardiovascular disease. Weight and blood pressure have been found to be associated in most studies in diverse populations. The increase or decrease of blood pressure with weight gain or loss suggests a causal relation, although the mechanism is uncertain. A correlation between blood pressure and weight can be identified early in life. This correlation coefficient increases to approximately 0.4 in young adults and then begins to decrease at older ages. It is likely that weight interacts with various factors controlling blood pressure at different points over a lifetime. The implications for prognosis or control of blood pressure at different ages may vary as well. Attention to minimizing weight gain at a particular period of life, such as in young adulthood, might have long-term beneficial effects in preventing subsequent hypertension or excess blood pressure increase with aging.
The effect of overfeeding on the body weight, body fat, water content, energy expenditure, and digestibility of energy and nitrogen was investigated over 42 days in six young men. The metabolic rates in standard situations of work and rest were determined. Energy intakes were apparently increased by 6.2 MJ/day and energy expenditure fell slightly by 0.3 MG/day during overfeeding. Fecal and urinary losses of energy were a similar proportion of the gross energy intake in control and overfeeding periods (8%). Metabolizable energy intakes calculated from food tables agreed well with values derived from digestibility measurements in the control period (mean difference = +2%) but not in the overfeeding period (+8%). The implications of this are discussed. Mean body weight gain was 6.0 kg, 10% of initial weight; mean fat gain was 3.7 kg and water gain 1.8 liter. There were considerable interindividual differences in the weight and fat gain for a given excess energy intake. Metabolic rates in standard tasks were 10% higher at the end of overfeeding but expressed as kilojoules per kilogram per minute were similar to control values. Mean energy gain (144 MJ = fat gain X 39 kJ/g) was less than excess energy intake even allowing for overestimation of intakes using food tables and increases in metabolic rate. Such a discrepancy is unlikely to be due to unmeasured increases in metabolic rate but could have arisen from errors in the calculation of the variables involved. In this study where moderate weight gains were achieved by overfeeding mainly fat, increases in metabolic rate appear to be associated with increased body size and tissue gain rather than a luxuskonsumption mechanism.
Resting metabolic rate (RMR) comprises 50-80% of daily energy expenditure, and is highly variable between subjects even after adjusting for body weight and body composition. RMR is believed to be genetically determined. Individuals with a low RMR for a given body size are at higher risk of significant weight gain, relative to those with a high RMR. Studies in Caucasians indicate that sympathetic nervous system (SNS) activity is related to the three major components of energy expenditure: RMR, the thermic effect of food and spontaneous physical activity. Pima Indians have low SNS activity and, unlike Caucasians, their RMR does not correlate with SNS activity. A variant of the beta 3-adrenoceptor gene has been found to be weakly associated with metabolic rate. Low resting SNS activity and its apparent dissociation from metabolic rate could be a causative factor in the development of obesity.
Given a specific research interest in human fatty acid metabolism, this article focuses primarily on the evidence surrounding the hypothesis that dysregulation of the fuel release function of fat cells (lipolysis) is an important contributing factor to the health hazards of obesity.