Article

Adaptive reduction in basal metabolic rate in response to food deprivation in humans: A role for feedback signals from fat stores

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

We assessed the importance of lean and fat tissue depletion as determinants of the adaptive reduction in basal metabolic rate (BMR) in response to food deprivation by reanalyzing the data on BMR and body composition for the 32 men participating in the classic Minnesota experiment of semi-starvation and refeeding. We used individual data on BMR, body fat, and fat-free mass (FFM) assessed during the control (prestarvation) period, at weeks 12 and 24 of semistarvation (S12 and S24), and week 12 of restricted refeeding (R 12) to calculate an index of the reduction in thermogenesis at S12, S24, and R12, defined as the change in BMR adjusted for changes in FFM and fat mass, and an index of the state of depletion of the fat mass and FFM compartments at these times, defined as the deviation in fat mass or FFM relative to control values. The results indicated a positive relation between the reduction in thermogenesis and the degree of fat mass depletion (but not FFM depletion) during weight loss as well as during weight recovery (r = 0.5, P < 0.01). Furthermore, the residual variance was predicted by the initial (prestarvation) percentage fat and the cormic index (sitting height/height). Taken together, these results in normal-weight men responding to severe food deprivation reveal anthropometric predictors for human interindividual variability in the capacity for energy conservation and suggest that the adaptive reduction in BMR is partly determined by an autoregulatory feedback control system linking the state of depletion of fat stores to compensatory mechanisms that suppress thermogenesis.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Indeed, in 2015, Dulloo and collaborators suggested that NW individuals might have a higher risk to experience post-WL 'fat overshooting' than people with obesity (12). This phenomenon is well illustrated in the Minnesota Starvation Experiment, in which 32 healthy NW males sustained a 24-week semistarvation, and lost an average of 25% of their initial BW (13)(14)(15). During weight recovery, adaptive thermogenesis and hyperphagia induced a fast rebound of fat mass (FM) (i.e. ...
... Data collection methods were judged strong for 56% (n = 10) of the articles while withdrawals and drop-out were considered as strong for 33% (n = 6). Finally, the global quality assessment was defined as strong for 6 studies (13)(14)(15)24,25,32), moderate for 9 studies (27,33-40), and weak for 3 studies (26,41,42). Individual quality assessment of the selected publications is detailed in Fig. 2. ...
... Two main study designs were identified among the 18 publications selected in the systematic review. Height studies (13)(14)(15)34,37-40) followed an interventional longitudinal protocol that involved a WL induced by diet from 3 weeks (34,37) to 24 weeks (13)(14)(15) duration in NW subjects, followed by a period of free-living or imposed recovery diet during 14 days (38) to 40 weeks (40) ( Table 1). Only one (40) of these studies included a control group without WL intervention, but results were thus not extracted as the mean BMI for this cohort was 27 kg/m² (overweight subjects). ...
Article
While there is an increasing prevalence of dieting in the overall population, weight loss practices could be a risk factor for weight gain in normal-weight individuals. The aim of the present work was to systematically review all the studies implicating diet restriction and body weight evolution in normal-weight people. The literature search was registered in PROSPERO (CRD42021281442) and was performed in three databases from April 2021 to June 2022 for articles involving healthy normal-weight adults. From a total of 1487 records initially identified, 18 were selected in the systematic review. Of the 8 dieting interventional studies, only one found a higher body weight after weight recovery, but 75% of them highlighted metabolic adaptations in response to weight loss favoring weight regain and persisting during/after body weight recovery. Eight of the 10 observational studies showed a relationship between dieting and major later weight gain while the meta-analysis of observational studies results indicated that ‘dieters’ have a higher body weight than ‘non-dieters’. However, considering the high methodological heterogeneity and the publication bias of the studies, this result should be taken with caution. Moreover, the term ‘diet’ was poorly described and we observed a large heterogeneity of the methods used to assess dieting status. Present results suggest that dieting could be a major risk factor for weight gain in the long term in normal-weight individuals. There is however a real need for prospective randomized controlled studies specifically assessing the relationship between weight loss induced by diet and subsequent weight in this population.
... It has been postulated to be a compensatory response that resists WL and promotes weight regain (12)(13)(14)(15) , but its influence on longer-term weight management has been recently questioned (16) . AT in resting EE (REE) has been previously documented in lifestyle (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) and surgical (34)(35)(36)(37)(38)(39) interventions. However, some studies have reported contrasting findings as they have not observed a significant value for AT (28,32,40) . ...
... Diet-only interventions. Eighteen studies using a diet-only intervention were included (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) . From those, one used a pharmacological therapy together with caloric restriction (32) . ...
... These studies involved 1780 participants (559 males). Only three studies had a mean BMI < 30 kg/m 2 (16,22,33) , while the majority of the studies included participants with obesity (17)(18)(19)(20)(21)(23)(24)(25)(26)(27)(29)(30)(31)(32) . The amount of weight lost varied between studies, with ten studies reporting a WL > 10 % (16)(17)(18)(19)(20)(21)(25)(26)(27)33) and seven reporting moderate WL (< 10 %) (22)(23)(24)(29)(30)(31)(32) . ...
Article
Full-text available
Adaptive thermogenesis (AT) has been proposed to be a compensatory response that may resist weight loss(WL) and promote weight regain. This systematic review examined the existence of AT in adults after a period of negative energy balance with or without a weight stabilization phase. Studies published until May 15th, 2020 were identified from PubMed, Cochrane Library, EMBASE, MEDLINE, SCOPUS and Web of Science. Inclusion criteria included: statistically significant WL; observational with follow-up or experimental studies; age>18years; sample size 10 participants; intervention period 1week; published in English; objective measures of total daily energy expenditure(TDEE), resting energy expenditure(REE) and sleeping energy expenditure(SEE). The systematic review was registered at PROSPERO(2020 CRD42020165348). A total of 33 studies comprising 2528 participants, were included. AT was observed in 27 out of 33 studies. Twenty-three studies showed significant values for AT for REE(82.8%), 4 studies for TDEE(80.0%) and 2 studies for SEE(100%). A large heterogeneity in the methods used to quantify AT and between subjects and among studies regarding the magnitude of WL and/or of AT was reported. Well-designed studies reported lower or non-significant values for AT. Overall, these findings suggest that although WL may lead to AT in some of the EE components, these values may be small or non-statistically significant when higher-quality methodological designs are used. Furthermore, AT seems to be attenuated, or non-existent, after periods of weight stabilization/neutral energy balance. Therefore, more high-quality studies are warranted not only to disclose the existence of AT, but to understand its clinical implications on weight management outcomes.
... Adaptive thermogenesis, assessed as reduction in BMR adjusted for FFM and fat mass at Weeks 4, 12, and 24 of semistarvation, was found to correspond to a reduction of about 10%, 20%, and 25% of prestarvation BMR, respectively. 64,89 Adapted from Keys et al. 1 and Dulloo. 75 (B) Pattern of changes in mean body weight and energy intake during the various phases of the MSE. ...
... The motivation and desire to provide a mechanistic explanation for these abovementioned phenomena of body composition dynamics have led to a series of revisits to the MSE data in mid-1990. [62][63][64] These were conducted against a background of earlier hypotheses that were built upon a reexamination of studies of prolonged fasting in men 65 refeeding. [66][67][68][69] The core features of these hypotheses were that body composition regulation during weight regain, to a large extent, would reflect the outcome of control systems that operate as a continuum of those occurring during weight loss, namely: ...
... Adaptive thermogenesis 64 Initial body fat (%) Initial Cormic index Fat depletion (sitting height/height) ( kg deficit as % kg initial) ...
Article
Since its publication in 1950, the Biology of Human Starvation, which describes the classic longitudinal Minnesota Experiment of semistarvation and refeeding in healthy young men, has been the undisputed source of scientific reference about the impact of long-term food deprivation on human physiology and behavior. It has been a guide in developing famine and refugee relief programs for international agencies, in exploring the effects of food deprivation on the cognitive and social functioning of those with anorexia nervosa and bulimia nervosa, and in gaining insights into metabolic adaptations that undermine obesity therapy and cachexia rehabilitation. In more recent decades, the application of a systems approach to the analysis of its data on longitudinal changes in body composition, basal metabolic rate, and food intake during the 24 weeks of semistarvation and 20 weeks of refeeding has provided rare insights into the multitude of control systems that govern the regulation of body composition during weight regain. These have underscored an internal (autoregulatory) control of lean-fat partitioning (highly sensitive to initial adiposity), which operates during weight loss and weight regain and revealed the existence of feedback loops between changes in body composition and the control of food intake and adaptive thermogenesis for the purpose of accelerating the recovery of fat mass and fat-free mass. This paper highlights the general features and design of this grueling experiment of simulated famine that has allowed the unmasking of fundamental control systems in human body composition autoregulation. The integration of its outcomes constitutes the "famine reactions" that drive the normal physiology of weight regain and obesity relapse and provides a mechanistic "autoregulation-based" explanation of how dieting and weight cycling, transition to sedentarity, or developmental programming may predispose to obesity. It also provides a system physiology framework for research toward elucidating proteinstatic and adipostatic mechanisms that control hunger-appetite and adaptive thermogenesis, with major implications for a better understanding (and management) of cachexia, obesity, and cardiometabolic diseases.
... Basal m etabolic rate is not a fixed entity but is variable and influenced by several factors, including: undem utrition (Grande et al. 1958), ovulatory status (Solom on et al. 1982;Snell et a l 1920;W akebam 1923), grow th (Talbot 1938), age, organ mass relative to body mass, organ growth rate (H olliday 1971, 1986; E lia 1992), fat stores (Dulloo andJacquet 1998, Garby andLam mert 1992), altitude (Lewis et al. 1943, Gill and Pugh 1964, H annon and Sudman 1973, tem perature and season (G ustafson and Benedict 1928, M ason 1934, Thom pson et al 1959, M ason and Jacob 1964, Park et al. 1969) disease state (Bose andDe, 1934, Elia 1992), and pregnancy and lactation (Khan and Belavady 1973, van Raaij et al. 1989, Heini et al. 1992, G oldberg et al. 1991. BM R changes during pregnancy as body com position changes and as efficiency in energy use increases. ...
... lean body m ass + fat mass + intercellular fluid mass). It is apparent that lean body mass is the best predictor for basal m etabolic rate and is closely tied to body com position (Grande and Keys 1980, Cunningham, 1982, R avussin and Bogardus 1986, R avussin et al. 1986, Owen et al. 1987, Garby et al. 1988, Lawrence et al. 1988, W einsier et al. 1992, Dulloo and Jacquet 1998. ...
... In an energy stressed population women are likely to employ energy saving mechanisms, such as those described in a Gambian population by Poppitt et al. (1993). She may reduce basal metabolism (see Dulloo and Jacquet 1998) and energy expenditure and increase her metabolic efficiency (Prentice et al. 1989, Poppitt et al. 1993). If this proves insuffiecient for meeting fetal energy needs, the fetus may adapt to energy stress by diverting energy resources from other systems to the brain (Dobbing and W iddowson 1965, Cheek et al. 1976, Dobbing 1976, Riopelle 1985, Holliday 1986. ...
Thesis
Full-text available
This thesis examines the relationship between growth, nutritional status, body composition and encephalisation in healthy fetuses and infants up to one year-of-age. It also compares human fetal brain and body growth patterns to those of baboons, rhesus monkeys and common marmosets, and assesses whether sex differences in encephalisation are present in these species during early life. A longitudinal in vivo study was undertaken where ultrasound measures of fetal biometry and anthropometric measures of infant biometry provided the basis for quantifying encephalisation and growth. Head circumference in early life was used as a proxy for brain size. In humans, skinfold thickness measures provided an index of nutritional status. The impact of maternal size, nutritional status and life history parameters were also considered in light of human offspring encephalisation, and the relationship between placenta weight and placental notching and offspring encephalisation was assessed. The effects on offspring encephalisation of maternal smoking and alcohol use during pregnancy were also examined and the implications of encephalisation for maternal-fetal conflict theory were considered. The relationship between the relative size of the brain and that of the other major organs was examined using fetal autopsy organ weight measures. The results demonstrated that intraspecific variation in encephalisation was marked in early life. At this time encephalisation was phenotypically flexible, with encephalisation SD scores undergoing regression to the mean over time. Upward or downward centile shifting in encephalisation related to previous head circumference size and growth. When catch up growth in head circumference occurred, corresponding catch down growth in body length occurred, characterising a trade-off in periodic increased growth between the brain and body. Encephalised neonates tended to be generally well-nourished with high fat and lean tissue deposits and relatively large non-brain organs. Human mothers who produced encephalised offspring had relatively large placentas with few placental notches. Maternal nutritional status further explained a significant but small amount of the variation in offspring encephalisation. Maternal smoking was shown to correlate with decreased neonatal encephalisation and maternal alcohol use was shown to correlate with decreased head circumference growth. Human fetal and infant males had relatively larger head circumferences than females (after controlling for body length differences between the sexes), with the degree of sexual dimorphism increasing over time. Non-human primate fetal encephalisation sexual dimorphism was also present but of a very low magnitude. The metabolic costs associated with human fetal and infant encephalisation sexual dimorphism were calculated to be low and did not represent a major additional energetic burden to the fetus or mother. Human fetal brain growth differed from that of baboons, rhesus monkeys and marmosets in being extended during both the hyperplasic and hypertrophic growth periods. Like the non-human primates, fetal brain growth began to slow in utero, but this occurred later in gestation in humans. Data from the literature showed that humans, cetaceans and pinnipeds differed from vertebrates in general in their increased body fatness which was associated with increased encephalisation. The findings of this thesis are also discussed within the context of evolutionary biology.
... This intrinsic control of lean-fat partitioning has been incorporated in a conceptual model of body composition autoregulation during weight recovery (shown in Fig. 3). It is constructed on the basis of results obtained from classic studies of starvation and recovery from starvation-in particular from the reanalysis of the several aspects of the Minnesota Experiment data on changes in body composition, food intake and basal metabolic rate [9,[12][13][14]. Its main features and operating modes are outlined below. ...
... (III) The adaptive suppression of thermogenesis that occurs during weight loss persists, at least in part, during weight recovery; its magnitude has been shown to be a specific function of the degree of fat mass depletion, but not that of FFM depletion [14]. This underscores the concept of a 'fat-stores memory' dictating an adipose-specific control of thermogenesis whose functional role is to accelerate specifically the body's fat reserves and not FFM, thereby contributing to a disproportionate rate of fat recovery relative to that of lean tissue. ...
... In humans, its existence is suggested from the reanalysis of data on dynamic changes in basal metabolic rate and body composition in the Minnesota Experiment. This showed that the reduction in mass-adjusted basal metabolic rate in response to weight loss was still present at the end of the 12-week phase of restricted refeeding, with the extent of this adaptive reduction in thermogenesis being specifically a function of fat mass depletion, but not that of FFM depletion [14]. A similar relationship between the magnitude of suppressed thermogenesis in the resting metabolic rate compartment and the recovery of fat mass (and not FFM) has been demonstrated in patients during nutritional rehabilitation from non-neoplastic gastrointestinal disease [18]. ...
Article
Full-text available
Collateral fattening refers to the process whereby excess fat is deposited as a result of the body's attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity.
... This is consistent with the theoretical equation developed earlier by Forbes [41] that quantified the non-linear relationship between the fat-free proportion of modest weight changes as a function of the initial body fat, and later extended by Hall [42] to account for the magnitude of body weight changes. (ii) An adaptive suppression of thermogenesis, which operates to conserve energy during weight loss, persists as a function of fat depletion during weight recovery and serves to accelerate specifically the recovery of fat mass but not that of FFM [43,45]. (iii) The hyperphagia during ad libitum refeeding is driven not only by the degree of fat depletion, but also by the degree of FFM depletion [46]. ...
... It should be noted, however, that excess dietary fat intake is unlikely to be the sole explanation for the asynchronous recovery of body fat vs. FFM in the Minnesota Experiment. Indeed, in the earlier phase of controlled refeeding lasting 12 weeks when dietary fat intake (in both absolute and relative terms) was actually lower than during the baseline period, a disproportionately faster recovery of body fat relative to FFM was also observed [35]; this was attributed to a sustained reduction of thermogenesis contributing to accelerated fat storage [43,45]. Overall, in our model presented here, it should be underlined that the parameter γ may not only depend upon the time factor and the period of time between cycling pattern but also upon dietary composition. ...
Article
Full-text available
The notion that dieting makes some people fatter has in the past decade gained considerable interest from both epidemiological predictions and biological plausibility. Several large-scale prospective studies have suggested that dieting to lose weight is associated with future weight gain and obesity, with such predictions being stronger and more consistent among dieters who are in the normal range of body weight rather than in those with obesity. Furthermore, the biological plausibility that dieting predisposes people who are lean (rather than those with overweight or obesity) to regain more body fat than what had been lost (referred to as fat overshooting) has recently gained support from a re-analysis of data on body composition during weight loss and subsequent weight recovery from the classic longitudinal Minnesota Starvation Experiment. These have revealed an inverse exponential relationship between the amount of fat overshot and initial adiposity, and have suggested that a temporal desynchronization in the recoveries of fat and lean tissues, in turn residing in differences in lean-fat partitioning during weight loss vs. during weight recovery (with fat recovery faster than lean tissue recovery) is a cardinal feature of fat overshooting. Within a conceptual framework that integrates the relationship between post-dieting fat overshooting with initial adiposity, the extent of weight loss and the differential lean-fat partitioning during weight loss vs. weight recovery, we describe here a mathematical model of weight cycling to predict the excess fat that could be gained through repeated dieting and multiple weight cycles from a standpoint of body composition autoregulation.
... 31 However, the majority of current weight loss interventions place the emphasis on food restriction rather than energy balance. regimens involving food restrictions tend to cause compensatory decreases in energy expenditure 32 and an increase in hunger. 33 a study of the national Weight control registry found that successful long-term weight loss maintainers (defined as average weight loss of 30 kg for an average of 5.5 years) engage in high levels of regular physical activity. ...
... 34 Strategies to prevent weight gain are more likely to be successful in the long term compared with strategies to promote weight loss because the physiologic systems involved in energy balance system respond more strongly to negative energy balance than to the prevention of positive energy balance. 32 Weight loss interventions trigger compensatory mechanisms to maintain energy balance. Since loss of body mass results in a decline in rMr, a 10 % weight loss can result in a reduction in calorie requirement of 170-250 kcal per day, and a 20 % weight loss requires a reduction of 325-480 kcal per days. ...
Article
Globally, bodyweight and obesity are rising in both the developing and developed world. To maintain a stable bodyweight, energy intake must, over time, exactly equal energy expenditure, a state known as energy balance. An understanding of the physiologic control of energy balance may be useful for designing interventions to tackle the obesity epidemic worldwide. Obesity occurs when the body's energy balance is positive (i.e. when energy intake exceeds energy expenditure). Human physiology is biased towards maintaining energy balance at high levels of energy intake and expenditure. As a result, strategies to combat obesity should include a focus on increasing physical activity along with strategies for modifying food intake. An understanding of energy balance leads to the conclusion that prevention of weight gain should be easier than treatment of obesity. Components of energy balance are interdependent, and weight loss requires major behaviour changes, which trigger compensatory decreases in energy expenditure that facilitate weight regain. Prevention of weight gain can be accomplished by smaller behaviour changes. In addition to being easier to sustain than larger behaviour changes, smaller ones produce less compensation by the energy balance regulatory system. It has been estimated that relatively small changes in energy intake and expenditure totaling 100 kcal per day could arrest weight gain in most people. Interventions that advocate small changes have shown promising levels of success.
... Carbohydrate, fat, protein, energy homeostasis and overfeeding [38,[84][85][86][87][88][89][90][91][92][93][94][95][96][97][98] Short-term and longer duration starvation studies [99,100] Physical activity of differential intensities and durations [66,[101][102][103][104][105][106] Intravenous lipid infusion studies [58,[85][86][87] Glucose bolus ingestion studies [107] Low/high fat, low/high carbohydrate diet studies [74,75,108,109] Insulinic/glycemic clamp studies [110] https://doi.org/10.1371/journal.pone.0192472.t003 ...
... DPP study averages for both placebo and lifestyle intervention arms [15] Study with large change in lifestyles [15,111] Study with dynamics of pancreatic decompensation [112,113] Study accounting for changes in metabolic rate with changes in FM and FFM [100,111,114,115] https://doi.org/10.1371/journal.pone.0192472.t004 meal-to-meal data and corresponding glycemic excursions were not available to us and we had to choose Cmax BLD hba1c as the best available proxy. ...
Article
Full-text available
A computational model of the physiological mechanisms driving an individual's health towards onset of type 2 diabetes (T2D) is described, calibrated and validated using data from the Diabetes Prevention Program (DPP). The objective of this model is to quantify the factors that can be used for prevention of T2D. The model is energy and mass balanced and continuously simulates trajectories of variables including body weight components, fasting plasma glucose, insulin, and glycosylated hemoglobin among others on the time-scale of years. Modeled mechanisms include dynamic representations of intracellular insulin resistance, pancreatic beta-cell insulin production, oxidation of macronutrients, ketogenesis, effects of inflammation and reactive oxygen species, and conversion between stored and activated metabolic species, with body-weight connected to mass and energy balance. The model was calibrated to 331 placebo and 315 lifestyle-intervention DPP subjects, and one year forecasts of all individuals were generated. Predicted population mean errors were less than or of the same magnitude as clinical measurement error; mean forecast errors for weight and HbA1c were ~5%, supporting predictive capabilities of the model. Validation of lifestyle-intervention prediction is demonstrated by synthetically imposing diet and physical activity changes on DPP placebo subjects. Using subject level parameters, comparisons were made between exogenous and endogenous characteristics of subjects who progressed toward T2D (HbA1c > 6.5) over the course of the DPP study to those who did not. The comparison revealed significant differences in diets and pancreatic sensitivity to hyperglycemia but not in propensity to develop insulin resistance. A computational experiment was performed to explore relative contributions of exogenous versus endogenous factors between these groups. Translational uses to applications in public health and personalized healthcare are discussed.
... Psychologists interested in reducing obesity should consider altering their approach. Why is a reduction in calorie intake recommended when a lower energy intake leads to hormonal changes that stimulate appetite (Lean & Malkova, 2016), reduces metabolic rate (Dulloo & Jacquet, 1998), and stimulates the consumption of more calorific foods (Benton, 2005)? Although it may appear to be common sense to suggest that eating less will reduce the risk of putting on weight, this may not be the optimal approach. ...
... There are other physiological changes. When food intake was restricted, the resulting loss of body fat was associated with a decrease in the production of body heat and a reduction in metabolic rate (Dulloo & Jacquet, 1998), changes that will facilitate a return to the initial weight. More generally, the perceived reward of food increased following weight loss (Cameron, Goldfield, Cyr, & Doucet, 2008). ...
Article
Full-text available
As the widespread availability of highly calorific food has resulted in a high incidence of obesity, attempts to decrease body weight have concentrated on trying to reduce energy intake. It is suggested that this is not the best approach. Although consuming more calories than expended is part of the initial problem, it does not follow that reducing intake, unless consciously counting calories, is the best solution. Mechanisms smooth out the large day-to-day differences in energy consumption, decreasing the importance of the size of a meal. In the short term a reduction in energy intake is counteracted by mechanisms that reduce metabolic rate and increase calorie intake, ensuring the regaining of lost weight. For example, even a year after dieting, hormonal mechanisms that stimulate appetite are raised. Over a million calories are consumed a year yet weight changes to only a small extent; there must be mechanisms that balance energy intake and expenditure. As obesity reflects only a small malfunctioning of these mechanisms, there is a need to understand the control of energy balance and how to prevent the regaining of weight after it has been lost. By itself, decreasing calorie intake will have a limited short-term influence.
... This suppression of metabolic rate then results in lowered body temperature and this may be causally linked to the observed lifespan effect [58]. These relationships have been inferred previously for rodents [48,59,60], nonhuman primates [25,61,62] and humans [63][64][65][66] when on CR protocols. On the other hand, the absence of any fat loss in the PR animals [35] does not lead to a reduction in leptin levels [41] resulting in no suppression of metabolic rate (confirmed here) and hence no lowering of body temperature [31] consistent with the absence of a lifespan effect at these levels of PR [50]. ...
... It is a nice and internally consistent story that matches aspects of the wider literature [25,47,48,[60][61][62][63][64][65][66] but our further analysis using more detailed body composition models suggests that it is wrong. When we explored the relationships between individual organ masses and the BMR our data showed some patterns consistent with previous such models. ...
Article
Full-text available
Under calorie restriction (CR) animals need to lower energy demands. Whether this involves a reduction in cellular metabolism is an issue of contention. We exposed C57BL/6 mice to graded CR for 3 months, measured BMR and dissected out 20 body compartments. From a separate age-matched group (n=57), we built 7 predictive models for BMR. Unadjusted BMR declined with severity of restriction. Comparison of measured and predicted BMR from the simple models suggested suppression occurred. The extent of 'suppression' was greater with increased CR severity. However, when models based on individual organ sizes as predictors were used, the discrepancy between the prediction and the observed BMR disappeared. This suggested 'metabolic suppression' was an artefact of not having a detailed enough model to predict the expected changes in metabolism. Our data have wide implications because they indicate that inferred 'metabolic' impacts of genetic and other manipulations may reflect effects on organ morphology.
... According to the results, 40% of the participants presented a RMR reduction above the estimated (metabolic adaptation). These participants were the ones who reduced FM the most, as reported in other studies 20,26,38 . ...
Article
Full-text available
Background: Diet and exercise are the mainstay of weight reduction programs. Aim: To evaluate the effect of diet and exercise on body weight and composition and resting metabolic rate (RMR) in obese adults. Material and Methods: Twenty-eight obese adults aged 22 to 61 years (18 women) completed four months of diet and exercise. They attended monthly nutritional consultations, and two-three weekly exercise sessions. At baseline and the end of the intervention, anthropometry, body composition by bioimpedance and RMR by indirect calorimetry (IC) were measured. Metabolic adaptation, defined as a decrease in thermogenesis to an extent greater than predicted based on the change in body weight and composition, was calculated. Results: Significant reductions in body weight and fat mass were observed in both genders. Fat-free mass decreased in women and remained unchanged in men. RMR remained stable. Metabolic adaptation was observed in 11/27 participants. Fat mass change in participants with and without metabolic adaptation was 8 Kg and 4,4 kg, respectively (p = 0,018). In the linear regression analysis, male sex accounted for a higher RMR (247.80 Kcal, p = 0,006) than females. For each kg of fat and fat free mass, the RMR varies 7.25 Kcal, (p = 0.02) and 9.79 Kcal (p = 0,006), respectively. Conclusions: The intervention reduced body weight and fat mass and maintained RMR. Fat free mass decreased in women. Participants with metabolic adaptation showed greater changes in fat mass.
... Starvation, the most severe form of malnutrition, can be caused by various socioeconomic, environmental, and medical factors [201]. Starvation can negatively affect bone quantity and quality through minerals, vitamins, and collagen type I deficiency [201,202]. There is a positive relationship between malnutrition during early life, or even in utero, and early incidence of osteoporosis and fractures [203][204][205][206][207]. ...
Article
Full-text available
Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis.
... Indeed, recent studies in humans have demonstrated that weight loss by caloric restriction results in a decline in basal metabolic rate (BMR), beyond changes attributed to decreased body weight [1,[4][5][6][7][8][9]. This adaptive reduction in BMR is a regulated mechanism that limits energy dissipation to conserve tissue mass, mostly by suppressing thermogenesis [10]. This adaptation highlights the ability to preserve energy balance when caloric intake is reduced [1]. ...
Article
Full-text available
Obesity results from an imbalance in energy homeostasis, whereby excessive energy intake exceeds caloric expenditure. Energy can be dissipated out of an organism by producing heat (thermogenesis), explaining the long-standing interest in exploiting thermogenic processes to counteract obesity. Mitochondrial uncoupling is a process that expends energy by oxidizing nutrients to produce heat, instead of ATP synthesis. Energy can also be dissipated through mechanisms that do not involve mitochondrial uncoupling. Such mechanisms include futile cycles described as metabolic reactions that consume ATP to produce a product from a substrate but then converting the product back into the original substrate, releasing the energy as heat. Energy dissipation driven by cellular ATP demand can be regulated by adjusting the speed and number of futile cycles. Energy consuming futile cycles that are reviewed here are lipolysis/fatty acid re-esterification cycle, creatine/phosphocreatine cycle, and the SERCA-mediated calcium import and export cycle. Their reliance on ATP emphasizes that mitochondrial oxidative function coupled to ATP synthesis, and not just uncoupling, can play a role in thermogenic energy dissipation. Here, we review ATP consuming futile cycles, the evidence for their function in humans, and their potential employment as a strategy to dissipate energy and counteract obesity.
... Reaching a weight plateau (Phase 3) can take many months to arrive at a new steady state with neutral energy balance and fully remodeled organs and tissues (81). Of the available literature describing metabolic features of people reaching Phase 3, post-obesity, some conclude that predicted and measured REE are approximately equal, whereas others report persistent metabolic adaptations, even during periods of weight regain (25,46,67,68,(82)(83)(84)(85)(86)(87)(88)(89)(90)(91). ...
Article
The basis of heat generated by the human body has been a source of speculation and research for more than 2,000 years. Basal heat production, now usually referred to as resting energy expenditure (REE), is currently recognized as deriving from biochemical reactions at subcellular and cellular levels that are expressed in the energy expended by the body’s 78 organs and tissues. These organs and tissues, and the 11 systems to which they belong, influence body size and shape. Connecting these subcellular‐/cellular‐level reactions to organs and tissues, and then on to body size and shape, provides a comprehensive understanding of individual differences in REE, a contemporary topic of interest in obesity research and clinical practice. This review critically examines these linkages, their association with widely used statistical and physiological REE prediction formulas, and often‐unappreciated aspects of measuring basal heat production in humans.
... Energy consumption will be lower than the energy requirement if breakfast is skipped before going to work. Food deprivation is known to cause a reduction in the basal metabolic rate (BMR) via compensatory metabolism [28]. The reduction in the BMR leads to the consumption of excess calories, ultimately leading to weight gain. ...
Article
Full-text available
Background The association between breakfast skipping and abnormal metabolic outcomes remains controversial. A comprehensive study with various stratified data is required. Objective The aim of this study was to investigate the relationship between abnormal metabolic outcomes and breakfast skipping by sex, age, and work status stratification. Methods We used data from the Korea National Health and Nutrition Examination Surveys from 2013 to 2018. A total of 21,193 (9022 men and 12,171 women) participants were included in the final analysis. The risk of metabolic outcomes linked to breakfast skipping was estimated using the negative binomial regression analysis by sex, work status, and age stratification. Results A total of 11,952 (56.4%) participants consumed breakfast regularly. The prevalence of abnormal metabolic outcomes was higher among those with irregular breakfast consumption habits. Among young male workers, negative binomial regression analysis showed that irregular breakfast eaters had a higher risk of abnormal metabolic outcomes, after adjusting for covariates (odds ratio, 1.15; 95% confidence interval, 1.03–1.27). Conclusions The risk of abnormal metabolic outcomes was significant in young men in the working population. Further studies are required to understand the association of specific working conditions (working hours or shift work) with breakfast intake status and the risk of metabolic diseases.
... Energy consumption will be lower than the energy requirement if breakfast is skipped before going to work. Food deprivation state is known to cause reduction in the basal metabolic rate (BMR) via compensatory metabolism (26). The reduction in the BMR leads to the consumption of excess calories, ultimately leading to weight gain. ...
Preprint
Full-text available
Background The association between breakfast skipping and abnormal metabolic outcome remains controversial. Large study with stratified data is needed. Objective The aim of the current study was to investigate the relationship between abnormal metabolic outcomes and breakfast skipping with sex, age, and work status stratification. Methods We used data from the Korea National Health and Nutrition Examination Surveys from 2013–2018. A total of 21,193 (9,022 men and 12,171 women) participants were included in the final analysis. The risk of the increased total number of metabolic outcomes linked to breakfast skipping was estimated using the Poisson regression analysis with sex, work status, and age stratification. Results A total of 11,952 (56.4%) participants consumed breakfast regularly. The prevalence of abnormal metabolic outcomes was higher among those with irregular breakfast consumption habits. In the irregular breakfast eating group, young men in the working population demonstrated a higher risk of metabolic syndrome after adjustment (odds ratio, 1.15; 95% confidence interval, 1.06–1.25). We found a similar association among middle-aged men in the working population (odds ratio, 1.11; 95% confidence interval, 1.05–1.19). Conclusions The risk of abnormal metabolic outcomes was significant in young men in the working population. Further studies are required to understand the association between specific working conditions (working hours or shift working) and breakfast intake status and the risk of metabolic outcomes
... It has been shown that energy balance is a dynamic process that involves factors that are beyond calorie counting. In fact, food restriction is not always the optimal solution for weight loss [3], as it is accompanied by compensatory mechanisms that lower energy expenditure and stores mobilization [4]. Additionally, energy intake is shown to be highly affected by the composition rather than the energy content of the diet [5]. ...
Article
Obesity and increased body adiposity have been alarmingly increasing over the past decades and have been linked to a rise in food intake. Many dietary restrictive approaches aiming at reducing weight have resulted in contradictory results. Additionally, some policies to reduce sugar or fat intake were not able to decrease the surge of obesity. This suggests that food intake is controlled by a physiological mechanism and that any behavioural change only leads to a short-term success. Several hypotheses have been postulated, and many of them have been rejected due to some limitations and exceptions. The present review aims at presenting a new theory behind the regulation of energy intake, therefore providing an eye-opening field for energy balance and a potential strategy for obesity management.
... Data from humans and mice suggest that homeostatic mechanisms exist to compensate when either energy intake or expenditure is perturbed to resist either weight gain or loss from an individual's initial set point [40][41][42][43]. Indeed, experimentally imposed alterations in body weight (either increased or decreased) results in a change in energy expenditure above or below that of individuals with a similar body composition, respectively, whose body weight was unaltered [41,44]. ...
Article
Full-text available
Obesity results from energy imbalance, when energy intake exceeds energy expenditure. Brown adipose tissue (BAT) drives non-shivering thermogenesis which represents a powerful mechanism of enhancing the energy expenditure side of the energy balance equation. The best understood thermogenic system in BAT that evolved to protect the body from hypothermia is based on the uncoupling of protonmotive force from oxidative phosphorylation through the actions of uncoupling protein 1 (UCP1), a key regulator of cold-mediated thermogenesis. Similarly, energy expenditure is triggered in response to caloric excess, and animals with reduced thermogenic fat function can succumb to diet-induced obesity. Thus, it was surprising when inactivation of Ucp1 did not potentiate diet-induced obesity. In recent years, it has become clear that multiple thermogenic mechanisms exist, based on ATP sinks centered on creatine, lipid, or calcium cycling, along with Fatty acid-mediated UCP1-independent leak pathways driven by the ADP/ATP carrier (AAC). With a key difference between cold- and diet-induced thermogenesis being the dynamic changes in purine nucleotide (primarily ATP) levels, ATP-dependent thermogenic pathways may play a key role in diet-induced thermogenesis. Additionally, the ubiquitous expression of AAC may facilitate increased energy expenditure in many cell types, in the face of over feeding. Interest in UCP1-independent energy expenditure has begun to showcase the therapeutic potential that lies in refining our understanding of the diversity of biochemical pathways controlling thermogenic respiration.
... The relationship between LBW and adiposity has been explained by several mechanisms. These are -the changes in the metabolic rate, 'adipose-specific control of thermogenesis', fall in the skeletal muscle glucose utilization leading to hyperglycemia and de novo lipogenesis and adipose tissue remodelling [37][38][39][40]. The thrifty phenotype and thrifty genotype hypotheses also contribute to the changes in the body composition of LBW children. ...
Article
Background: India has a high prevalence of low birth weight. Evidence indicates that poor fetal growth and rapid postnatal weight gain are associated with adiposity. Objectives: (i) To study the differences between the anthropometry, body fat measures of LBW and NBW children and (ii) To find out if there is any relationship between birth weight, change in weight SD and body fat measures of these children. Study design: Cross-sectional study. Subjects: We studied 396 children aged between 3.5 and 4 years who were beneficiaries of government-run anganwadis in urban slums of Mumbai city, India. Outcome measures: Birth weight, current weight, height, skinfold thicknesses and waist circumference. Change in weight SD and body fat (%) were calculated. WHOAnthro was used to compute the z scores. Parent's education, income and breastfeeding history was recorded. Results: The mean change in weight SD of LBW and NBW groups were 1.01 ± 1.4 and -0.73 ± 1.13 respectively (p < 0.001). LBW children were lighter and shorter than NBW ones but had similar body fat (%) and central adiposity measures. In LBW and NBW children, birth weight Z score and change in weight SD were positively related to body fat (%) and waist circumference. Conclusion: Children in this study belonged to low socioeconomic section. Despite this, LBW displayed a tendency towards accumulating body fat particularly, abdominal fat for lower body weight. Birth weight and postnatal weight change predict body fat and waist circumference in LBW and NBW children.
... This finding is consistent with earlier reports demonstrating that FM change but not FFM change was positively correlated with starvation-induced metabolic adaptation. (29) More recent work has demonstrated that reduction of fat energy stores below a critical threshold triggers metabolic adaptation. (30,31) In the current study, subjects with NAFLD had a greater baseline FM and a greater fraction of weight loss was in the form of FM compared to subjects without NAFLD. ...
Article
Full-text available
Weight loss is the primary intervention for nonalcoholic fatty liver disease (NAFLD). A decrease in resting metabolic rate (RMR) out of proportion to the degree of weight loss may promote weight regain. We aimed to determine the impact of hepatic steatosis on weight loss‐associated changes in RMR and metabolic adaptation, defined as the difference between predicted and measured RMR after weight loss. We retrospectively analyzed prospectively collected data from 114 subjects without diabetes (52 with NAFLD), with body mass index (BMI) >35, and who enrolled in a 6‐month weight loss intervention. Hepatic steatosis was determined by unenhanced computed tomography scans by liver:spleen attenuation ratio
... As part of a plethora of adaptations during energy restriction, resting energy expenditure (REE) and physical activity are also affected. Studies performed in lean and obese subjects have shown significant reductions in REE during and shortly after weight loss to values below predictions based on weight loss and body composition changes (Leibel et al., 1995a;Doucet et al., 2001;Dulloo and Jacquet, 1998;Schwartz and Doucet, 2010;Tremblay and Chaput, 2009;Weyer et al., 2000;Martin et al., 2007). The decrease in REE beyond what can be predicted by the loss of fat-free mass (FFM) and fat mass (FM), is defined as adaptive thermogenesis. ...
Article
Full-text available
Background: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). Methods: 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters. Results: The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss. Conclusion: Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.
... Because metabolic rate reflects the use of food energy to conduct biological work, the availability of food energy to burn (e.g. recently acquired food and/or stored energy) could play an important role in explaining this variation, at least at the individual level. For example, food deprivation or the presence of competitors can decrease food uptake, leading to reduced metabolic rates (Dulloo & Jacquet, 1998;DeLong et al., 2014). Furthermore, feeding and activity levels can influence the body mass scaling of metabolic rate, as different activities have different energy costs (Glazier, 2010;DeLong & Hanley, 2013). ...
Article
1. Metabolism is the fundamental process that powers life. Understanding what drives metabolism is therefore critical to our understanding of the ecology and behaviour of organisms in nature. 2. Metabolic rate generally scales with body size according to a power law. However, considerable unexplained variation in metabolic rate remains after accounting for body mass with scaling functions. 3. We measured resting metabolic rates (oxygen consumption) of 227 field‐caught wolf spiders. Then, we tested for effects of body mass, species, and body condition on metabolic rate. 4. Metabolic rate scales with body mass to the 0.85 power in these wolf spiders, and there are metabolic rate differences between species. After accounting for these factors, residual variation in metabolic rate is related to spider body condition (abdomen:cephalothorax ratio). Spiders with better body condition consume more oxygen. 5. These results indicate that recent foraging history is an important determinant of metabolic rate, suggesting that although body mass and taxonomic identity are important, other factors can provide helpful insights into metabolic rate variation in ecological communities.
... There is substantial experimental data to suggest that the body defends more strongly against a negative energy balance than a positive balance [72,73]; therefore, it may be easier to prevent against weight not yet acquired than to lose existing weight [74,75]. Given the lack of success many adults experience losing weight and maintaining weight loss, a more achievable strategy to reduce the prevalence of overweight and obesity may be to prevent weight gain. ...
Chapter
In this chapter we review the evidence from prospective cohort studies and randomized controlled trials that consider the interactions between physical activity (PA), cardiorespiratory fitness (CRF), and obesity. Furthermore, we consider the interaction between these variables and obesity-related health outcomes. We observe that in prospective studies both PA and CRF are inversely associated with obesity and obesity-related health outcomes. Based on evidence from randomized controlled trials, we highlight the importance of PA for weight management and improvement in CRF, dyslipidemia, insulin resistance, and hypertension. Finally, we conclude with an overview of current PA recommendations for improving CRF and reducing obesity, as well as a discussion on the importance of PA and CRF as clinically relevant measures beyond obesity management.
... While attenuation of the decline in REE has been observed with some IER protocols when compared to CER, it remains to be seen whether these dietary regimes also result in minimisation of some of the other adaptive responses associated with ER. Under some circumstances, a number of the adverse metabolic and hormonal outcomes associated with weight loss have been reported to be quickly reversed upon restoration of EB, namely normalisation of fasting and postprandial energy expenditure, and circulating levels of leptin and thyroid [107][108][109][110][111][112][113]. In one trial among postmenopausal women, following 10 days of ER (3350 kJ per day), reductions in body composition-adjusted REE and circulating levels of thyroid hormones were returned to baseline after 10 days in EB [114]. ...
Article
Full-text available
Athletes utilise numerous strategies to reduce body weight or body fat prior to competition. The traditional approach requires continuous energy restriction (CER) for the entire weight loss phase (typically days to weeks). However, there is some suggestion that intermittent energy restriction (IER), which involves alternating periods of energy restriction with periods of greater energy intake (referred to as ‘refeeds’ or ‘diet breaks’) may result in superior weight loss outcomes than CER. This may be due to refeed periods causing transitory restoration of energy balance. Some studies indicate that intermittent periods of energy balance during energy restriction attenuate some of the adaptive responses that resist the continuation of weight and fat loss. While IER—like CER—is known to effectively reduce body fat in non-athletes, evidence for effectiveness of IER in athletic populations is lacking. This review provides theoretical considerations for successful body composition adjustment using IER, with discussion of how the limited existing evidence can be cautiously applied in athlete practice.
... In fact, through the compilation of a systematic review, we reported that resting energy expenditure was reduced by~15 kcal per kg lost (18) when all types of interventions are considered. An increasing number of research groups have contributed to the documentation of decreases in energy expenditure that are greater than what would be expected from the changes in body mass and composition (23)(24)(25)(26). What is more, this depression in energy expenditure seemingly persists after weight loss (27)(28)(29). ...
Article
Obesity is an extremely resilient condition. Weight loss is most challenging, and weight recidivism is rampant. There is accumulating evidence highlighting that energy deficits meant to produce increased mobilization of energy stores trigger a number of somewhat persistent adaptations that together increase the drive to eat and decrease energy output. These adaptations ostensibly enable a context where the likelihood of energy compensation is heightened. In fact, energy compensation is present for both diet and exercise induced energy deficits although at different magnitudes. For the most part, the energy compensation in response to exercise induced energy deficits seems to be larger. Interestingly, energy compensation appears to be greater for longer interventions, an effect independent of whether the energy deficit is induced through diet or exercise. The latter suggests that the increased drive to eat and the reduced energy expenditure that accompany weight loss might be successfully fought off initially. However, with time there seems to be increasing erosion of the behaviours that initially opposed adaptations to weight loss and increased energy compensation progressively sets in. Under such conditions, it would seem prudent to propose weight loss targets that align with a level of behaviour modifications that can be sustained indefinitely.
... Some animals reduce their background levels of oxygen consumption in response to food restriction either in the laboratory [57,58] or in a natural context [59,60], presumably to elongate the period of time before they would reach emaciation. This has also been observed, albeit subtly, in humans [61,62]. ...
Article
The obesity epidemic in humans is juxtaposed by observations of passerine birds exhibiting fine-scale body mass regulation. The ecology literature is replete with research into why these animals regulate body weight, citing tradeoffs between competing pressures such as emaciation and predation. Yet studies on the underlying mechanisms of mass regulation in these animals are scarce. Maintaining or decreasing weight could obviously be achieved by limiting food intake. However, there are numerous reasons why an animal may not control ingestion, at least precisely. This Opinion article investigates the plausibility of possible behavioural and physiological mechanisms to adaptively maintain or decrease body mass in birds and other animals. Candidate behavioural mechanisms include exercising and fidgeting, while physiological mechanisms could include reducing digestive efficiency or mitochondrial efficiency.
... Previous studies suggest that FM is an independent contributor to RMR [28À31]. The link between FM and RMR is possibly due to the compensatory responses involved in energy homeostasis triggered by changes of adipose tissue [31]. The individual with high body fatness normally has an adaptive increase of RMR that depends on the sympathetic nervous system (SNS) and acts to limit weight gain [32]. ...
Article
Objectives: It has been demonstrated that leptin influences the energy balance by regulating appetite and increasing energy expenditure (EE). However, the relationship between circulating leptin and EE is confounded owing to variations in body composition. The aim of this study was to determine the role of circulating leptin in energy regulation and to examine whether the leptin-mediated changes in EE are associated with adiposity among healthy adults living in Singapore. Methods: We conducted a cross-sectional study of 300 participants (112 men). Resting metabolic rate (RMR) was measured by indirect calorimetry. Body composition (i.e., fat mass [FM] and fat-free mass [FFM]) was measured by dual-energy x-ray absorptiometry. Serum leptin levels were determined by radioimmunoassay. Results: There were strong correlations between circulating leptin levels, FM, and RMR in healthy men and women. After normalization of RMR by a power function model (kcal·kg FFM0.86·d-1), the influence of FFM can be effectively removed. The normalized RMR was significantly associated with both FM (r = 0.28, P < 0.001) and log leptin (r = 0.35, P < 0.001). In the stepwise multiple regression analysis, leptin level is the major predictor for normalized RMR, accounting for 12% of the variation. In contrast, FM did not explain any variation in normalized RMR. Conclusion: Leptin may be a more significant predictor of normalized RMR than FM per se. The contribution of FM to RMR could be via a mechanism that is related to leptin-dependent responses involved in energy homeostasis.
... A direct comparison of each developmental stage revealed no difference 124 between F control groups and starvation-selected S groups in the transition from egg to first instar larvae, 125 suggesting the selection protocol does not affect the earliest stages of development (data not shown). In addition to delayed development, reduced metabolic rate provides a mechanism for conserving energy 141 (Dulloo and Jacquet, 1998;Ma and Foster, 1986). Animals, including Drosophila, reduce metabolic rate 142 under starvation conditions (Crabtree, 1990;McCue, 2010;Wang et al., 2006), suggesting that modulation 143 of metabolic rate may promote starvation resistance. ...
Preprint
Full-text available
Food shortage represents a primary challenge to survival, and animals have adapted diverse developmental, physiological, and behavioral strategies to survive when food becomes unavailable. Starvation resistance is strongly influenced by ecological and evolutionary history, yet the genetic basis for the evolution of starvation resistance remains poorly understood. The fruit fly, Drosophila melanogaster , provides a powerful model for leveraging experimental evolution to investigate traits associated with starvation resistance. While control populations only live a few days without food, selection for starvation resistances results in populations that can survive weeks. We have previously shown that selection for starvation resistance results in increased sleep and reduced feeding in adult flies. Here, we investigate the ontogeny of starvation resistance-associated behavioral and metabolic phenotypes in these experimentally selected flies. We find that selection for starvation resistance results in delayed development and a reduction in metabolic rate in larvae that persists into adulthood, suggesting that these traits may allow for the accumulation of energy stores and an increase in body size within these selected populations. In addition, we find that sleep is largely unaffected by starvation- selection and that feeding increases during the late larval stages, suggesting that experimental evolution for starvation resistance produces developmentally specified changes in behavioral regulation. Together, these findings reveal a critical role for development in the evolution of starvation resistance and indicate that selection can selectively influence behavior during defined developmental timepoints. SUMMARY STATEMENT Drosophila melanogaster selected for starvation resistance take longer to develop and exhibit development-specific changes in traits associated with the accumulation and conservation of energy stores.
... However, this theory does not accord with the general experience of individuals when dieting. Furthermore, under the settling point model, we would not expect to see any compensatory changes in energy expenditure or intake to resist changes in energy balanceyet such changes are routinely observed (Norgan and Durnin, 1980;Leibel et al., 1995;Horton et al., 1995;Dulloo et al., 1997;Dulloo and Jacquet, 1998;Goldberg et al., 1998;Weyer et al., 2001;Galgani and Santos, 2016;Hall et al., 2011Hall et al., , 2012Johannsen et al., 2012;Polidori et al., 2016). A review of 32 controlled feeding studies in humans concluded that the responses were most consistent with the set-point rather than the settling point model (Hall and Guo, 2017). ...
Article
Full-text available
Human obesity has a large genetic component, yet has many serious negative consequences. How this state of affairs has evolved has generated wide debate. The thrifty gene hypothesis was the first attempt to explain obesity as a consequence of adaptive responses to an ancient environment that in modern society become disadvantageous. The idea is that genes (or more precisely, alleles) predisposing to obesity may have been selected for by repeated exposure to famines. However, this idea has many flaws: for instance, selection of the supposed magnitude over the duration of human evolution would fix any thrifty alleles (famines kill the old and young, not the obese) and there is no evidence that hunter-gatherer populations become obese between famines. An alternative idea (called thrifty late) is that selection in famines has only happened since the agricultural revolution. However, this is inconsistent with the absence of strong signatures of selection at single nucleotide polymorphisms linked to obesity. In parallel to discussions about the origin of obesity, there has been much debate regarding the regulation of body weight. There are three basic models: the set-point, settling point and dual-intervention point models. Selection might act against low and high levels of adiposity because food unpredictability and the risk of starvation selects against low adiposity whereas the risk of predation selects against high adiposity. Although evidence for the latter is quite strong, evidence for the former is relatively weak. The release from predation ∼2-million years ago is suggested to have led to the upper intervention point drifting in evolutionary time, leading to the modern distribution of obesity: the drifty gene hypothesis. Recent critiques of the dual-intervention point/drifty gene idea are flawed and inconsistent with known aspects of energy balance physiology. Here, I present a new formulation of the dual-intervention point model. This model includes the novel suggestion that food unpredictability and starvation are insignificant factors driving fat storage, and that the main force driving up fat storage is the risk of disease and the need to survive periods of pathogen-induced anorexia. This model shows why two independent intervention points are more likely to evolve than a single set point. The molecular basis of the lower intervention point is likely based around the leptin pathway signalling. Determining the molecular basis of the upper intervention point is a crucial key target for future obesity research. A potential definitive test to separate the different models is also described.
... 7 WL induces metabolic adaptations that decrease energy expenditure and increase appetite, aiming to revert body mass back to pre-diet values. 8 The regained mass is preferentially fat, 9 suggesting that metabolic changes in subcutaneous adipose tissue (SAT) are important regulators of post-dieting physiology. Previous studies in SAT have reported several cellular metabolic pathways, especially lipid and mitochondrial metabolism, as downregulated during caloric restriction. ...
Article
Full-text available
Objectives: We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities. Methods: SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography. Results: Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss. Conclusions: Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it. Data availability: The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.International Journal of Obesity accepted article preview online, 05 December 2017. doi:10.1038/ijo.2017.299.
... Il est reconnu qu'une perte de poids entraîne une diminution de la dépense énergétique de repos, la principale composante de la dépense énergétique totale [14] . Outre la perte de masse maigre associée à la perte pondérale qui contribue majoritairement à la baisse de la dépense énergétique, la perte de masse adipeuse contribue partiellement à la réduction de la dépense énergétique de repos [15] . En général, la perte pondérale induite par restriction énergétique se compose d'environ 70 % de masse grasse et de 30 % de masse maigre [16] . ...
... In two intervention studies on weight loss, aligned with the present study results, the physical activity (along with calorie intake limitation or without it) resulted in fat-free mass gain and fat tissue loss, while BMI did not show the significant changes. [25,26] Moreover, Evans et al. reported that small changes in BF percent may not be accurately reflected in BMI. [27] In a longitudinal study of white children, there was a direct relationship between total BF-free mass index and BMI percentile, whereas FM index and BF percent had more complicated relationships with BMI percentile depending on gender and age and whether BMI percentile was high or low. ...
... In two intervention studies on weight loss, aligned with the present study results, the physical activity (along with calorie intake limitation or without it) resulted in fat-free mass gain and fat tissue loss, while BMI did not show the significant changes. [25,26] Moreover, Evans et al. reported that small changes in BF percent may not be accurately reflected in BMI. [27] In a longitudinal study of white children, there was a direct relationship between total BF-free mass index and BMI percentile, whereas FM index and BF percent had more complicated relationships with BMI percentile depending on gender and age and whether BMI percentile was high or low. ...
Article
Full-text available
Background: Obesity in adolescence is the strongest risk factor for obesity in adulthood. This study aimed to evaluate the effects of a comprehensive lifestyle intervention on different anthropometric indices in 12.16.year.old boy adolescents after 12 Weeks of Intervention. Methods: A total of 96 male adolescents from two schools participated in this study. The schools were randomly assigned to intervention (53 students) and control school (43 students). Height and weight of students were measured and their body mass index (BMI) was calculated. Body fat percent (BF) and body muscle percent (BM) was assessed using a bioimpedance analyzer considering the age, gender, and height of students at baseline and after intervention. The obesity reduction intervention was implemented in the intervention school based on the Ottawa charter for health promotion. Results: Twelve weeks of intervention decreased BF percent in the intervention group in comparison with the control group (decreased by 1.81% in the intervention group and increased by 0.39% in the control group, P < 0.01). However, weight, BMI, and BM did not change significantly. Conclusions: The result of this study showed that a comprehensive lifestyle intervention decreased the body fat percent in obese adolescents, although these changes was not reflected in the BMI. It is possible that BMI is not a good indicator in assessment of the success of obesity management intervention.
... Although the pathway of influence of PA on adiposity is known, [5,6] the mechanism of physical fitness in maintaining energy balance and attenuating adiposity remains unclear at this time [3,7,8]. Speculatively, increased fat-free mass can raise energy expenditure above and beyond the energy burned during vigorous physical activity (VPA) [9]. Furthermore, it has been observed that energy expenditure remains elevated after high-intensity exercise sessions [10,11]. ...
... Based on recent scientific evidence, our program included a combination of physical exercises to improve CRF and MuS. Both modalities can contribute to maintaining the fat-free mass metabolically active when combined with a low calorie diet, especially the modality of MuS exercises, thus avoiding the reduction in the basal metabolic rate induced by diet (Dulloo and Jacquet, 1998). Some authors have pointed out that MuS exercises specifically contribute to increasing fat-free mass (Sothern et al., 2000) and that they play a fundamental role in preventing post-intervention weight gain (Schwingshandl et al., 1999). ...
Article
Full-text available
Few studies have evaluated the changes in physical fitness (PF) of obese children and adolescents of a physical activity program for the treatment of obesity, and even fewer have explored the modality of home-based physical exercise. The objective of this study is to evaluate the changes in PF and body composition (BC) of a home-based physical exercise for treating childhood obesity. Thirty-three overweight/obese children and adolescents participated for six months in a home-based intervention that combined aerobics and muscular strength exercises. The results were compared, before and after the intervention, for the different PF components (VO2max, abdominal muscle resistance strength, and lower body explosive strength) and BC (body mass index Z-score (BMI-Z), percentage of body fat, and fat-free mass) variables. A significant reduction was observed in the percentage of body fat (4.7%) and the BMI-Z score (.23), and there was an increase in the fat-free mass of 2.9 kg (p < .001). In addition, the VO2max showed a significant increase (p < .05). The results of the different strength tests also showed significant improvements (p < .05). Our findings support the effectiveness of this program improving not only BC but also PF. However, our results should be interpreted with caution due to lack of control group.
... From the data collected during a subsequent stay in a respiratory chamber, their losses in body weight were found to be accompanied by a markedly lower SPA, which like their diminished daily EE, was found to persist several months after the onset of weight recovery and which could be implicated in their disproportionate regain of body fat relative to lean mass. These findings are therefore consistent with the notion that diminished SPA may contribute significantly to the adaptive suppression of thermogenesis that occurs in response to caloric restriction and weight loss and that drives rapid fat storage during weight regain (49)(50)(51). ...
Article
Isometric thermogenesis as applied to human energy expenditure refers to heat production resulting from increased muscle tension. While most physical activities consist of both dynamic and static (isometric) muscle actions, the isometric component is very often essential for the optimal performance of dynamic work given its role in coordinating posture during standing, walking and most physical activities of everyday life. Over the past 75 years, there has been sporadic interest into the relevance of isometric work to thermoregulatory thermogenesis and to adaptive thermogenesis pertaining to body-weight regulation. This has been in relation to (i) a role for skeletal muscle minor tremor or microvibration – nowadays referred to as ‘resting muscle mechanical activity’ – in maintaining body temperature in response to mild cooling; (ii) a role for slowed skeletal muscle isometric contraction–relaxation cycle as a mechanism for energy conservation in response to caloric restriction and weight loss and (iii) a role for spontaneous physical activity (which is contributed importantly by isometric work for posture maintenance and fidgeting behaviours) in adaptive thermogenesis pertaining to weight regulation. This paper reviews the evidence underlying these proposed roles for isometric work in adaptive thermogenesis and highlights the contention that variability in this neglected component of energy expenditure could contribute to human predisposition to obesity.
Article
Objective To determine and compare the dose–response effects of exercise and caloric restriction on visceral adipose tissue in overweight and obese adults, while controlling for the weekly energy deficit induced by the interventions. Methods PubMed, Embase, CINAHL and Web of Science were searched for randomised controlled trials comparing exercise or caloric restriction against eucaloric controls in overweight or obese adults. The primary outcome was the change in visceral fat measured by CT or MRI. Meta-analyses and meta-regressions were performed to determine the overall effect size (ES) and the dose–dependent relationship of exercise and caloric restriction on visceral fat. Heterogeneity, risk of bias and the certainty of evidence were also assessed. Results Forty randomised controlled trials involving 2190 participants were included. Overall, exercise (ES −0.28 (−0.37 to −0.19); p<0.001; I ² =25%) and caloric restriction (ES −0.53 (−0.71 to −0.35); p<0.001; I ² =33%) reduced visceral fat compared with the controls. Exercise demonstrated a dose–response effect of −0.15 ((−0.23 to −0.07); p<0.001) per 1000 calories deficit per week, whereas the effect of caloric restriction was not dose-dependent (ES 0.03 (−0.12 to 0.18); p=0.64). Most of the studies showed a moderate risk of bias. Conclusions These findings support the dose–dependent effects of exercise to reduce visceral fat in overweight and obese adults. Caloric restriction did not demonstrate a dose–response relationship, although this may be attributed to the smaller number of studies available for analysis, compared with exercise studies. PROSPERO registration number CRD42020210096.
Preprint
In the present study, novel methods were developed which allowed continuous (24/7) measurement of blood pressure (BP) and renal blood flow (RBF) in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. The study determined the effects of a high salt (HS) diet upon whole kidney O2 consumption and the metabolomic profiles of normal Sprague Dawley (SD) rats. A separate group of rats was studied to determine changes in the cortex (Cx) and outer medulla (OM) tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to a 4.0% NaCl diet. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. Increased glycolysis was evident with the elevation of mRNA expression encoding key glycolytic enzymes and release of pyruvate and lactate from the kidney in the renal venous blood. Glycolytic production of NADH is used in either the production of lactate or oxidized via the malate aspartate shuttle. Aerobic glycolysis (e.g., Warburg-effect) may account for the needed increase in cellular energy. The study provides interesting and provocative new data of how normal kidneys respond to a HS diet and guides us toward deeper mechanistic studies examining the effects of a HS diet upon kidney metabolism.
Article
PurposeThe present study examined the changes in and risk factors for body composition (BC) during the first postoperative month when dynamic biological reactions occur.Methods We retrospectively assessed 202 patients who underwent gastrectomy. The BC was assessed using a bioelectrical impedance analysis and evaluated within 1 month preoperatively, 1 week postoperatively, and 1 month postoperatively. Multiple regression analyses were performed to identify predictive factors for BC change.ResultsThe mean reduction rate in BC at 1 month postoperatively was − 6.0, − 10.5, − 5.6, − 1.1, − 10.1, and + 1.2% for body weight, body fat, skeletal muscle, bone mineral, extracellular water/total body water, and the whole-body phase angle, respectively. A multiple regression analysis revealed that independent risk factors for weight loss were complications, operative time, and type of gastrectomy (P = 0.004, 0.011, 0.015, respectively), and those for skeletal muscle loss were complications and gastrectomy type (P = 0.002, 0.010, respectively). A segmental lean mass analysis revealed that the lower limbs were markedly reduced at 1 week postoperatively (− 8.0%), and these independent risk factors were the female sex and Stage II/III disease (P = 0.008, 0.036, respectively).Conclusion Detailed analyses of BC might help elucidate the mechanisms underlying postoperative physical changes, which might be useful for perioperative management.
Article
Full-text available
The observation that 64% of English adults are overweight or obese despite a rising prevalence in weight-loss attempts suggests our understanding of energy balance is fundamentally flawed. Weight-loss is induced through a negative energy balance; however, we typically view weight change as a static function, in that energy intake and energy expenditure are independent variables, resulting in a fixed rate of weight-loss assuming a constant energy deficit. Such static modelling provides the basis for the clinical assumption that a 14644 kJ (3500 kcal) deficit translates to a 1 lb weight-loss. However, this ‘3500 kcal (14644 kJ) rule’ is consistently shown to significantly overestimate weight-loss. Static modelling disregards obligatory changes in energy expenditure associated with the loss of metabolically active tissue, i.e. skeletal muscle. Additionally, it disregards the presence of adaptive thermogenesis, the underfeeding-associated fall in resting energy expenditure beyond that caused by loss of fat-free mass. This metabolic manipulation of energy expenditure is observed from the onset of energy restriction to maintain weight at a genetically pre-determined set point. As a result, the observed magnitude of weight-loss is disproportionally less, followed by earlier weight plateau, despite strict compliance to a dietary intervention. By simulating dynamic changes in energy expenditure associated with underfeeding, mathematical modelling may provide a more accurate method of weight-loss prediction. However, accuracy at an individual level is limited due to difficulty estimating energy requirements, physical activity and dietary intake in free-living individuals. In the present paper, we aim to outline the contribution of dynamic changes in energy expenditure to weight-loss resistance and weight plateau.
Article
Ancel Keys, whose life spanned over 100 years (1904–2004), made a wealth of seminal scientific and public health contributions. As a physiologist, nutritionist, and public health scientist, he has left his mark on the 20th century by exploring different areas of physiology and nutrition, as well as by contributing to the understanding of basic public health issues. Among his major achievements one can mention in chronological order: studying adaptation to very high altitude, developing the K ration to enable the US military to survive with light but dense food, dissecting the physiology of starvation and nutritional rehabilitation to optimize recovery of functions, uncovering the link between serum cholesterol and heart disease, coordinating the first multi‐country epidemiological longitudinal study in nutrition and health, coining the word “body mass index” (BMI), which he showed to be the best body weight index to predict body fat, and promoting the Mediterranean diet for a healthy life style. This review examines the historical events and scientific intrigues that have surrounded Ancel Keys's major classical studies that have ensured him a central place in the history of medical science.
Article
Weight disorders are strikingly prevalent globally and can contribute to a wide array of potentially fatal diseases spanning from type II diabetes to coronary heart disease. These disorders have a common cause: poor calorie balance. Since energy expenditure (EE) [kcal/day] constitutes one half of the calorie balance equation (the other half being food intake), its measurement could be of great value to those suffering from weight disorders. A technique for contact free assessment of EE is presented, which only relies on CO2 concentration monitoring within a sealed office space, and assessment of carbon dioxide production rate (VCO2). Twenty healthy subjects were tested in a cross-sectional study to evaluate the performance of the aforementioned technique in measuring both resting energy expenditure (REE) and exercise energy expenditure using the proposed system (the "SmartPad") and a U.S. Food and Drug Administration (FDA) cleared gold standard reference instrument for EE measurement. For VCO2 and EE measurements, the method showed a correlation slope of 1.00 and 1.03 with regression coefficients of 0.99 and 0.99, respectively, and Bland-Altman plots with a mean bias = -0.232% with respect to the reference instrument. Furthermore, two subjects were also tested as part of a proof-of-concept longitudinal study where EE patterns were simultaneously tracked with body weight, sleep, stress, and step counts using a smartwatch over the course of a month, to determine correlation between the aforementioned parameters and EE. Analysis revealed moderately high correlation coefficients (Pearson's r) for stress (raverage=0.609) and body weight (raverage=0.597) for the 2 subjects. The new Smart Pad method was demonstrated to be a promising technique for energy expenditure measurement under free-living conditions.
Chapter
Starvation is a multifaceted condition commonly encountered by surgeons. The inability to ingest sufficient calories and/or an appropriate mixture of nutrients results in changes in the underlying metabolic milieu that can affect the outcome of both illnesses and their treatments. Organisms undergo a systematic adaptive response to starvation wherein there is preservation of protein mass and the utilization of fat stores for energy. Prolonged starvation (>30 days) eventually results in death from myocardial infarction, pneumonia, or organ failure. Semistarvation, insufficient energy and/or protein intake, is also commonly encountered in the perioperative period.
Article
The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs lean mass recovery, with this phenomenon of 'preferential catch-up fat' being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (Tc) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill® system - with the telemetry capsules implanted in the peritoneal cavity - was used for continuous monitoring of Tc for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24h Tc was reduced in response to semistarvation (-0.77°C, p<0.001), and remained significantly lower than in controls during the catch-up fat phase of refeeding (-0.27°C on average, p<0.001); the lower Tc during refeeding being more pronounced during the light phase than during the dark phase of the 24h cycle (-0.30°C vs -0.23°C, p<0.01), and with no between-group differences in locomotor activity. A lower 24h Tc in animal showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e. at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery, and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body's fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth.
Book
Fatigue is a condition spanning the breadth of human functioning in health and disease and is a central concern in sport and exercise. Even so we are yet to fully understand its causes. One reason for this lack of understanding is that we seldom consider fatigue from an evolutionary perspective - as an adaptation that provided reproductive success. This ground-breaking book outlines the evidence that fatigue is a result of adaptations distinctive to humans. It argues that humans developed adaptations which led to enhanced fatigue resistance compared with other mammals and discusses the implications in the context of exercise, health and performance. Highly illustrated throughout, it covers topics such as defining and measuring fatigue, the emotional aspect of fatigue, how thermoregulation affects the human capacity to resist fatigue, and fatigue in disease. Human Fatigue is essential reading for all exercise scientists as well as graduate and undergraduate students in the broad field of physiology and exercise physiology.
Article
Food shortage represents a primary challenge to survival, and animals have adapted diverse developmental, physiological and behavioral strategies to survive when food becomes unavailable. Starvation resistance is strongly influenced by ecological and evolutionary history, yet the genetic basis for the evolution of starvation resistance remains poorly understood. The fruit fly Drosophila melanogaster provides a powerful model for leveraging experimental evolution to investigate traits associated with starvation resistance. While control populations only live a few days without food, selection for starvation resistance results in populations that can survive weeks. We have previously shown that selection for starvation resistance results in increased sleep and reduced feeding in adult flies. Here, we investigate the ontogeny of starvation resistance-associated behavioral and metabolic phenotypes in these experimentally selected flies. We found that selection for starvation resistance resulted in delayed development and a reduction in metabolic rate in larvae that persisted into adulthood, suggesting that these traits may allow for the accumulation of energy stores and an increase in body size within these selected populations. In addition, we found that larval sleep was largely unaffected by starvation selection and that feeding increased during the late larval stages, suggesting that experimental evolution for starvation resistance produces developmentally specified changes in behavioral regulation. Together, these findings reveal a critical role for development in the evolution of starvation resistance and indicate that selection can selectively influence behavior during defined developmental time points.
Data
Full-text available
Model parameters estimated from diabetes related studies. (PDF)
Data
Full-text available
Model parameters estimated using data from healthy metabolic studies. (PDF)
Article
Full-text available
Aim: to estimate the resting energy expenditure (REE) of organ tissue components using Dual Energy x-ray Absorptiometry (DXA) in pubertal boys. The mass of components and REE were compared among groups of different nutritional statuses. Methods: a sample of 278 boys (13.7 ± 2.4 years old) was grouped according to BMI nutritional status for Brazilian children and adolescents¹ such as Underweight (UW), Normal weight (NW), Overweight (OW), and Obese (OB). The REE of organ tissue components given by DXA was calculated using specific models for skeletal muscle tissue (SMT), adipose tissue (AT), bone tissue (BT) and residual tissue (RT) based on previous reports. The absolute and relative REE (REEDXA) of each component were statistically compared among groups. Results: No differences of total REEDXA were found among nutritional groups (F(3, 274)=0.071, p=0.976). When, however, specific REE was considered per component, differences were found for BT and REEBT between NW-OW (p=0.003) and NW-OB (p=0.048); in AT and REEAT for all the groups (p<0.001), except between UW-NW (p=1.000); in RT and REERT between NW-OB (p=0,022) and SMT and REESMT (p=0,039). Greater proportions of organ tissue of RT and high metabolic rates, were observed in the UW group (78.3%) in comparison to the OB group (60.7%). Conclusion: This approach provides a new opportunity to examine energy metabolism for individual differences of pediatric populations. It is an applicable strategy both to prescribe exercises and to administer diets to this population, as it reveals the magnitude of heat-producing body components.
Chapter
This chapter outlines the assessment of the patient for nutrition support and then discusses the most efficacious method(s) to provide the nutrition. The initiation of nutrition support depends upon the type of nutrition that can be delivered (parenteral vs enteral nutrition), the nutritional state of the patient, along with their current disease state. Parenteral nutrition is valuable in breaking the cycle of malabsorption and malnutrition to allow for regeneration of digestive function in extremely depleted patients. Patients with severe short bowel syndrome (SBS) require parenteral support. Enteral nutrition is the standard of care when it comes to delivering nutrition to a patient with severe acute pancreatitis. With the assistance of home care companies, both enteral and parenteral feeding can be managed at home. This excludes well-nourished patients who only required temporary nutritional support during their hospitalization and were able to resume their usual oral intake.
Article
Full-text available
Body composition was studied in severely undernourished adult male inhabitants of a rural area of Colombia to evaluate the extent and the time course of the changes occurring upon nutritional repletion. During a 45-day basal period on a low (26g/day) protein diet containing adequate calories, body fat depots increased significantly (mean +/- SD = +3.02 +/- 2.9 kg), and there was a significant decrease in cell hydration from 81.8 to 76.4% (-5.4 +/- 9.1%). Upon protein repletion (100 g/day), cell hydration decreased significantly to 71.4%, while body cell mass increased markedly (9.0 +/- 1.1 kg). During protein repletion, muscle cell mass increased significantly (+5.5 +/- 0.6 kg) and rapidly, while the increase in nonmuscle cells (+3.5 +/- 3.8 kg) and specifically in red cell mass lagged behind. With repletion, the changes in the absolute values for plasma volume (+0.4 +/- 0.13 liters) were significant, but those in extracellular fluid volume (-0.7 +/- 1.9 liters) were not. Thus, the major compositional changes observed occurred in the body fat and the body cell mass components; these occurred independently of each other.
Article
Full-text available
On the basis of literature values, the relationship between fat-free mass (FFM), fat mass (FM), and resting energy expenditure [REE (kJ/24 h)] was determined for 213 adults (86 males, 127 females). The objectives were to develop a mathematical model to predict REE based on body composition and to evaluate the contribution of FFM and FM to REE. The following regression equations were derived: 1) REE = 1265 + (93.3 x FFM) (r2 = 0.727, P < 0.001); 2) REE = 1114 + (90.4 x FFM) + (13.2 x FM) (R2 = 0.743, P < 0.001); and 3) REE = (108 x FFM) + (16.9 x FM) (R2 = 0.986, P < 0.001). FM explained only a small part of the variation remaining after FFM was accounted for. The models that include both FFM and FM are useful in examination of the changes in REE that occur with a change in both the FFM and FM. To account for more of the variability in REE, FFM will have to be divided into organ mass and skeletal muscle mass in future analyses.
Article
Full-text available
Although attempted weight loss is common, little is known about the goals and durations of weight loss attempts and the rates of achieved weight loss in the general population. Data were collected by telephone in 1989 from adults aged 18 years and older in 39 states and the District of Columbia. Analyses were carried out separately for the 6758 men and 14,915 women who reported currently trying to lose weight. Approximately 25% of the men respondents and 40% of the women respondents reported that they were currently trying to lose weight. Among men, a higher percentage of Hispanics (31%) than of Whites (25%) or Blacks (23%) reported trying to lose weight. Among women, however, there were no ethnic differences in prevalence. The average man wanted to lose 30 pounds and to weigh 178 pounds; the average woman wanted to lose 31 pounds and to weigh 133 pounds. Black women wanted to lose an average of 8 pounds more than did White women, but Black women's goal weight was 10 pounds heavier. The average rate of achieved weight loss was 1.4 pounds per week for men and 1.1 pounds per week for women; these averages, however, may reflect only the experience of those most successful at losing weight. Attempted weight loss is a common behavior, regardless of age, gender, or ethnicity, and weight loss goals are substantial; however, obesity remains a major public health problem in the United States.
Article
Full-text available
The relation between change in resting metabolic rate (RMR) and change in fat-free mass (FFM) after weight loss is not well understood and is often inappropriately expressed in kilocalories per unit of FFM. We measured RMR and FFM in 35 obese patients enrolled in a conservative weight-loss program. RMR per kilogram FFM was not different after weight loss. However, the regression of delta RMR on delta FFM revealed that the decline in RMR tended to be greater than could be accounted for by loss of FFM. At initial test and retest, body fat (Fat) was not a predictor of RMR after FFM had been taken into account but delta Fat significantly contributed to the prediction of delta RMR when added to the equation after delta FFM. Thus, people losing larger amounts of weight had declines in RMR greater than could be accounted for by loss of FFM. Self-reported age of onset of obesity was not related to delta RMR.
Article
Full-text available
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.
Article
Full-text available
The magnitude of metabolic adaptation to malnutrition is still debated and few studies have investigated the phase of recovery from malnutrition. The aim of the present work was to determine whether refeeding was associated with adaptive changes in 1) energy expenditure, 2) maximal capacity for oxidizing lipids, and 3) whole-body protein turnover. Eleven malnourished patients with nonneoplastic gastrointestinal diseases were studied by using indirect calorimetry and L-[1-13C]leucine infusion while being infused with lipid-rich total parenteral nutrition (TPN). The same study was performed before initiation of TPN and after a mean gain of 6.5 kg body wt. In absolute values, resting energy expenditure (REE) increased after refeeding (4.05 +/- 0.85 compared with 4.60 +/- 1.05 MJ/d). Change in REE adjusted for fat-free mass (FFM) correlated significantly with change in body weight (r = 0.850, P = 0.01) and change in body fat (r = 0.798, P = 0.01) but not with change in FFM (r = -0.06, NS). Lipid oxidation decreased significantly after body weight gain (0.93 +/- 0.28 compared with 0.50 +/- 0.37 mg.kg-1.min-1). When expressed per kg FFM, protein turnover and breakdown increased significantly during body weight gain. Moreover, the change in protein turnover correlated with the rate of change in FFM, suggesting that FFM accretion requires increased interorgan exchange of amino acids. Our data suggest that in patients similar to those studied here and during recovery from malnutrition, the degree of change in adjusted REE during refeeding is correlated with change in fat mass and not with change in FFM, and that there is a decrease in oxidation of infused lipids. These mechanisms may contribute to body fat repletion and regulation during weight gain.
Article
An increase in the sensation of hunger and overeating after a period of chronic energy deprivation can be part of an autoregulatory phenomenon attempting to restore body weight. To gain insights into the role of fat and lean tissue depletion as determinants of such a hyperphagic response in hu- mans, we reanalyzed the individual data on food intake and body composition available for the 12 starved and refed men in the classical Minnesota Experiment after a shift from a 12-wk period of restricted refeeding to an ad libitum refeeding period of 8 wk. For each individual, the following were determined: 1) the total hyperphagic response during the ad libitum refeeding period, cal- culated as the energy intake in excess of that during the prestar- vation (control) period: 2) the degree of fat recovery and that of fat-free-mass (FFM) recovery before ad libitum refeeding, calcu- lated as the deviation in fat and FFM from their respective pre- starvation values (ie, the amount of fat or FFM before ad libitum refeeding as a percentage of fat or FFM during the control period); and 3) the deficit in energy intake before ad libitum refeeding, calculated as the difference between the energy intake during the period of restricted refeeding and that during the control period. The results indicate that 1) the total hyperphagic response is inversely correlated with the degree of fat recovery (r = -0.6) as well as with that of FFM recovery (r = -0.5), 2) the correlation between hyperphagia and FFM recovery persists after adjustment for fat recovery, and 3) the correlations between hyperphagia and fat recovery or FFM recovery persist after adjustment for the variance in the energy deficit during the preceding period of restricted refeeding. Taken together, these results in humans sug- gest that poststarvation hyperphagia is determined to a large extent by autoregulatory feedback mechanisms from both fat and lean tissues. These findings, which have implications for both the treatment of obesity and for nutritional rehabilitation after malnu- trition and cachexia, have been integrated into a compartmental model of autoregulation of body composition, and can be used to explain the phenomenon of poststarvation overshoot in body fat. Am J C/in Nutr 1997:65:717-23.
Article
The extent to which the resting and nonresting components of 24-hour energy expenditure decrease after weight reduction has not been prospectively assessed in ambulatory, weight-stable, reduced-obese humans. Accordingly, 24-hour energy expenditure was estimated as the weight-stabilizing (±50 g/d) daily caloric intake of a defined liquid diet in a cross-sectional study of ten reduced-obese subjects after a 23.2% ± 9.4% weight loss and 18 obese subjects at baseline weight. A regression analysis demonstrated an 18% decrease in the mean daily energy requirement of the reduced-obese subjects compared with that of subjects of the same relative body weight who had never dieted. Strong linear relationships were noted between estimated 24-hour energy expenditure and fat-free mass (FFM), and between resting metabolic rate (RMR) and FFM in the subjects at baseline weight. In six reduced-obese men, the 24-hour energy expenditure was only 75.7% ± 5.6% of the value predicted by regression analysis for the decreased FFM. In these six subjects the RMR was 97.4% ± 7.5% of that predicted for the decreased FFM, suggesting that essentially all the energy savings relative to FFM in the reduced-obese state occurred in nonresting energy expenditure. In a subsequent group of seven subjects studied longitudinally before and after a 21.5% ± 2.3% weight loss, the decrease in nonresting energy expenditure accounted for 582 ± 276 kcal/d or 71% of the decrease in estimated 24-hour energy expenditure. These data suggest a decrease in the nonresting energy expenditure of ambulatory reduced-obese individuals, which is greater than previously appreciated. A substantial increase in physical activity would be necessary in any weight loss maintenance program to overcome the energy savings of the reduced-obese state.
Article
Basal metabolic rate (BMR) has been reported to decrease during semistarvation and during hypocaloric treatment of obesity. However, it remains controversial whether the decrease is due to change in body composition, or if it represents a downregulation in cellular metabolism. To examine this relationship, we reviewed studies of BMR in children, adolescents, adults, semistarved non-obese, anorexics, and weight-reducing obese. The relationship between BMR and fat-free mass (FFM) of children, lean adolescents, and lean and obese adults consuming sufficient energy could be described by a single line, BMR (MJ/d) = 2.44 + 0.084 FFM (SEE = 0.63, R2 = .80). Obese adolescents demonstrated BMRs greater than predicted and semistarved lean individuals demonstrated BMRs less than predicted by this relationship. Obese individuals demonstrated a reduced BMR during underfeeding, but less so than semistarved lean individuals. The reduction in BMR relative to FFM in semistarved lean individuals could not be explained by disproportionate reductions in body cell mass (BCM).
Article
Differences in body composition have often been examined in conjunction with measurements of energy expenditure in men and women. Numerous studies during the past decade examined the relationship between resting energy expenditure (REE) and the components of a two-compartment model of composition, namely the fat-free mass (FFM) and the fat mass (FM). A synthetic review of these studies confirms a primary correlation between REE and FFM in adults over a broad range of body weights. A generalized prediction equation is proposed as REE = 370 +/- 21.6 x FFM. This equation explains 65-90% of the variation in REE. Several studies suggest, further, that FFM predicts total daily energy expenditure (TDEE) equally well. An independent contribution by FM to the prediction of either REE or TDEE is not supported for the general population, perhaps reflecting the relative constancy of the absolute FM in nonobese individuals. In the subset of obese women, FM may be a significant predictor.
Article
In this study, six obese women received a very-low-calorie diet (VLCD) for 3 wk. At day 0, body composition was assessed with a bioelectric impedance analyzer. The evolution in lean body mass (LBM) during the VLCD was estimated from nitrogen balance, measuring urine and fecal losses and taking into account skin, nitrate, and menstrual losses to avoid underestimation bias that could explain the decreased ratio of resting metabolic rate (RMR) to LBM previously reported. RMR was measured at days 0, 3, 5, and 21. The RMR-LBM ratio declined significantly during the VLCD period and decreased faster during the first week; the day 3, day 5, and day 21 ratio values were 94%, 91%, and 82%, respectively, of the original. The RMR-LBM ratio decrease after 21 d of a VLCD was near that found in chronic undernutrition. Results of previous studies that did not find any drop in the RMR-LBM ratio in obese adults on VLCDs might be explained by their LBM-assessment methods.
Article
Malnutrition occurs commonly in patients with acquired immunodeficiency syndrome (AIDS). The efficacy of nutritional support is unknown. A prospective, longitudinal study was conducted to determine the effect of prolonged total parenteral nutrition on body composition in 12 AIDS patients. Five patients were malnourished because of problems with food intake or absorption, while seven had systemic infections, with or without a malabsorption syndrome. The AIDS patients gained body weight and body fat content in response to total parenteral nutrition, while mean body cell mass, estimated as total body potassium content, was unchanged. However, all five patients with altered intake or absorption had significant repletion of body cell mass which was significantly different from the patients with systemic infections. Calorie and nitrogen intake did not differ between the two groups. It is concluded that body mass repletion is possible in AIDS patients in whom malabsorption is the major pathogenetic factor in producing malnutrition and is less successful in patients with serious ongoing systemic diseases. Thus, the response to nutritional support is dependent on the particular clinical circumstances.
Article
Adaptive changes in energy expenditure to changes in energy intake are far less than previously believed once changes in body weight and physical activity are taken into account. Alterations in metabolic efficiency of +/- 10% in total energy expenditure are the limits of what can normally be expected on prolonged under- or overfeeding. The supposed twofold variation in energy requirements of adults is based on measurements of food intake, which, despite involving weighted intakes over a week, cannot be considered realistic. Subtle differences in the energetic responses to fat, protein, and carbohydrate signify the different effective energetic contribution of isoenergetic substrates and may account for the propensity to obesity in individuals and societies on a high-fat diet.
Article
Studies in this report investigate the existence and quantitative contribution of a metabolic component to an apparently elevated efficiency of energy utilization during refeeding following low-calorie consumption. Energy balance during a 25-d refeeding period was assessed in rats that had been food restricted (at 50% of normal intake) for either 30 or 10 d. Relative to weight-matched controls (with comparable lean tissue mass and similar food intake), refeeding following both periods of low food consumption (30 or 10 d) was associated with a 10% reduction in energy expenditure (p less than 0.001). Analysis of body composition revealed that virtually all the energy saved as a result of this metabolic (as opposed to tissue mass) adaptation was deposited as fat rather than protein. After the energy cost for depositing the extra fat is accounted for, the metabolic component represents a net 15% lower energy expenditure when normal food intake is resumed. These adaptive changes in energy expenditure may thus constitute an important mechanism for the rapid replenishment of energy stores in preparation for recurring food shortages and may also underlie the ease with which the obese condition is rapidly reachieved after weight loss.
Article
It is current clinical practice to give intravenous nutrition (IVN) to critically ill postoperative septic intensive care patients to prevent loss of body protein, although it has not hitherto been possible to confirm this by direct measurement of body composition. Using a neutron activation analysis facility adapted to provide an intensive care environment and tritiated water dilution we directly measured total body water, protein and fat before and after 10 days of IVN (mean daily non-protein energy and amino acid intakes 2,750 kcal and 127 gm) in eight adult intensive care patients. All patients had recovered from the septic shock syndrome but were still ventilator dependent at the start of IVN. Six patients survived to leave hospital. As a group, the patients lost 12.5% of body protein (mean loss 1.5 +/- SE 0.3 kg; p = 0.001) despite a gain in fat (mean 2.2 +/- 0.8 kg; p = 0.026). There were, in addition, large losses of body water in most patients (mean, 6.8 +/- 2.6 kg; p = 0.036). We conclude that substantial losses of body protein occur in critically ill septic patients despite aggressive nutritional support and that further research is urgently required on the fate of infused substrates and the efficacy of alternative nutritional therapies.
Article
Body composition studies were performed in 33 patients suffering from the acquired immunodeficiency syndrome (AIDS). Studies included measurements of total body potassium, fat, and total body and extracellular water volumes plus serum retinol binding protein concentration, iron binding capacity, and albumin concentration. AIDS patients were underweight (p less than 0.001) and were depleted of potassium (p less than 0.001) with the lowest values occurring in patients close to death at the time of study. Body fat contents also were reduced. Intracellular water volumes were decreased in the AIDS patients (p less than 0.001) with a relative increase in extracellular water volume (p less than 0.001). Serum protein concentrations were decreased in the AIDS patients. Longitudinal studies did not demonstrate tissue repletion in patients with AIDS, despite apparent clinical stability. These studies demonstrate that severe, progressive malnutrition occurs in patients with AIDS. If malnutrition can be shown to have a deleterious effect upon the disease course, therapy of malnutrition may play an important role in the treatment of this disorder.
Article
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.
Article
Ingested metabolizable energy was partitioned into 3 components--storage, cost of storage, and maintenance--to study energy utilization during 20 days of refeeding following a 3-day fast in adult male Wistar rats. During the refeeding period, one experimental group was refed ad libitum, whereas two others were restricted to approximately 75 and 50%, respectively, of prefast food intake. Energy utilization in the experimental groups was compared with that in nonfasted controls. Energy conservation occurred in all experimental groups during refeeding, and the primary form of that conservation was a decrease in the energy required for maintenance. The decreased requirement for maintenance allowed a greater proportion of ingested energy to be used for restoration of carcass energy. The degree of energy conservation was, in general, proportional to the degree of food restriction during refeeding.
Article
Recent studies of the treatment of obesity by moderate and severe caloric restriction show that patients treated in randomized trials using a conventional 1200 kcal/d reducing diet, combined with behavior modification, lose approximately 8.5 kg in 20 weeks. They maintain approximately two thirds of this weight loss 1 year later. Patients treated under medical supervision using a very-low-calorie diet (400 to 800 kcal/d) lose approximately 20 kg in 12 to 16 weeks and maintain one half to two thirds of this loss in the following year. Both dietary interventions are associated with increasing weight regain over time, although regain can be minimized with the recognition that obesity, in many cases, is a chronic condition that requires continuing care. Patients who participate in a formal weight-loss maintenance program, exercise regularly, or both are likely to achieve the best long-term results.
Article
To gain insights into the control systems underlying human variability in the regulation of body composition during weight recovery, as well as the disproportionate recovery of fat relative to lean tissue, the classical Minnesota Experiment conducted on 32 men subjected to long-term semi-starvation and refeeding was revisited with the following objectives: (1) to determine whether the control of energy-partitioning between lean and fat tissues during weight loss and weight recovery is an individual characteristic, and if a predictor can be statistically identified, (2) to determine whether the reduction in thermogenesis during weight loss persists during weight recovery, and underlies the disproportionate recovery of fat tissue and (3) to integrate the control of energy-partitioning and that of thermogenesis in order to explain the pattern of lean and fat tissue mobilisation and deposition during weight loss and weight recovery. Individual data on body weight, body fat, fat-free-mass (FFM), and basal metabolic rate (BMR), assessed during the control baseline period (i.e. prior to weight loss), at the end of 24 weeks of semi-starvation, and at the end of a 12 week period of restricted refeeding, were used to calculate the following parameters: (i) a quantitative index of energy-partitioning, the P-ratio, defined as the proportion of body energy mobilised as protein during weight loss, or as the proportion of body energy deposited as protein during weight recovery, (ii) a quantitative index of changes in thermogenesis, defined as the change in BMR adjusted for FFM (or for both FFM and fat mass) and (iii) the degree of replenishment of fat and FFM compartments, defined as the recovery of body fat and FFM (during refeeding) as a percentage of that lost during semi-starvation. This re-analysis indicates the following: (i) a large inter-individual variability in P-ratio during both weight loss and weight recovery, but for a given individual, the P-ratio during refeeding is strongly correlated with the P-ratio during semi-starvation, (ii) body composition during the control period is the most important predictor of variability in P-ratio, such that the higher the initial % body fat, the lower the proportion of energy mobilised as protein, and hence the greater the propensity to mobilise fat during semi-starvation and to subsequently deposit fat during refeeding and (iii) at week 12 of refeeding, the change in adjusted BMR is found to be reduced by a magnitude which is inversely proportional to the degree of fat recovery, but is unrelated to the degree of FFM recovery. A quantitative relationship is derived between the P-ratio during refeeding, the % fat recovery, and the P-ratio during semi-starvation. Evidence is presented here suggesting that (i) human variability in the pattern of lean and fat tissue deposition during weight recovery is to a large extent determined by individual variations in the control of energy-partitioning, for which the initial % body fat is the most important predictor and (ii) the disproportionate gain in fat relative to lean tissue during weight recovery is contributed by a reduction in thermogenesis (i.e. increased efficiency of food utilization) for accelerating specifically the replenishment of the fat stores. These control systems, operating via energy-partitioning and thermogenesis, have been integrated into a compartmental model for the regulation of body composition during underfeeding/refeeding, and can be used to explain the individual pattern of lean and fat tissue deposition during weight recovery in situations ranging from the rehabilitation after malnutrition to the relapse of obesity.
Article
Studies of experimental starvation that were carried out in healthy volunteers during the first half of this century often provide an invaluable source of 'untapped' data. The motivation and desire to gain a better insight into the regulation of body composition by re-analysing these data in the light of more 'modern' concepts of energy partitioning and thermogenesis become irresistible when similar studies can no longer be performed in humans, if only for ethical reasons. This paper brings together new findings, largely centered upon recent re-analysis of data from the classical studies of experimental starvation, semi-starvation and refeeding, and proposes a theory of regulation of body composition during weight recovery in which the cardinal features rest upon three auto-regulatory control systems. These control systems--operating via energy partitioning and two distinct forms of adaptive thermogenesis--have been integrated into a compartmental model for the autoregulation of body composition during cycles of underfeeding/refeeding. This model can be used to explain the individual pattern of lean and fat tissue deposition during weight recovery in situations ranging from rehabilitation after malnutrition/cachexia to the relapse of obesity. It also provides a framework of 'system physiology' for integrating the advances in molecular biology into this area of nutritional energetics.
Human body composition: growth, aging, nutrition and activity
  • Gb Forbes
Forbes GB. Human body composition: growth, aging, nutrition and activity. New York: Springer-Verlag, 1987.