Targeting lifestyle energy expenditure in the management of obesity and health: from biology to built environment.

Increasing lifestyle energy expenditure has long been advocated in the prevention and treatment of obesity, as embodied in the ancient prescription of Hippocrates (the 'father of modern medicine') that people with obesity should eat less and exercise more. However, the long-term outcome of exercise alone or in combination with dieting in obesity management is poor. To understand the reasons underlying these failures and to develop novel strategies that target lifestyle energy expenditure in both prevention and treatment of obesity, research over the past decades has focused on (i) the interactions between physical activity and body weight (and its composition) throughout the lifespan; (ii) the influence of biology and potential compensatory changes in energy expenditure, food intake and food assimilation in response to energy deficits; and (iii) the impact of the built environment (outdoor and indoor) and smart technology on physical activity behaviours, thermoregulatory thermogenesis and metabolic health. It is against this background that recent advances relevant to the theme of 'Targeting Lifestyle Energy Expenditure in the Management of Obesity and Health: From Biology to Built Environment' are addressed in this overview and the nine review articles in this supplement, reporting the proceedings of the 9th Fribourg Obesity Research Conference.

Do gender and ethnic differences in fasting leptin in Indians and Creoles of Mauritius persist beyond differences in adiposity?

Recent body composition studies on the island of Mauritius in young adults belonging to the two main ethnicities-Indians (South Asian descent) and Creoles (African/Malagasy descent)-have shown gender-specific ethnic differences in their body mass index (BMI)-Fat% relationships. We investigated here whether potential gender and ethnic differences in blood leptin would persist beyond that explained by differences in body composition. In healthy young adult Mauritian Indians and Creoles (79 men and 80 women; BMI range: 15-41 kg m-2), we investigated the relationships between fasted serum leptin with BMI, waist circumference (WC), total fat% assessed by deuterium oxide dilution technique and central adiposity (trunk fat%) assessed by abdominal bioimpedance analysis. The results indicate that the greater elevations in leptin-BMI and leptin-WC regression lines in women compared with men, as well as in Indian men compared with Creole men, are abolished when BMI and WC are replaced by total body fat% and trunk fat%, respectively. In women, no significant between-ethnic difference is observed in total body fat%, trunk fat% and serum leptin. Thus, in young adult Mauritians, a population at high risk for later cardiometabolic diseases, the differences in body fat% entirely accounted for the observed gender and ethnic differences in serum leptin.

Nutrition, movement and sleep behaviours: their interactions in pathways to obesity and cardiometabolic diseases.

Among the multitude of dietary and lifestyle behaviours that have been proposed to contribute to the obesity epidemic, those that have generated considerable research scrutiny in the past decade are centred upon sleep behaviours, sedentary behaviours (sitting or lying while awake) and diminished low-level physical activities of everyday life, with each category of behaviours apparently presenting an independent risk for obesity and/or cardiometabolic diseases. These behaviours are highly complex, operate in synergy with each other, disrupt the link between regulation of the circadian clock and metabolic physiology and impact on various components of daily energy expenditure and feeding behaviours to promote obesity and hinder the outcome of obesity therapy. As such, this behavioural triad (nutrition, movement and sleep) presents plenty of scope for intervention and optimization in the context of body weight regulation and lifestyle-related disease prevention. It is against this background that recent advances relevant to the theme of 'Nutrition, Movement & Sleep Behaviors: their interactions in pathways to obesity and cardiometabolic diseases' are addressed in this overview and the nine review articles in this supplement reporting the proceedings of the 8th Fribourg Obesity Research Conference.

Isometric thermogenesis at rest and during movement: a neglected variable in energy expenditure and obesity predisposition.

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.

Body composition-derived BMI cut-offs for overweight and obesity in Indians and Creoles of Mauritius: comparison with Caucasians.

BACKGROUND AND AIMS: Global estimates of overweight and obesity prevalence are based on the World Health Organisation (WHO) body mass index (BMI) cut-off values of 25 and 30 kg m-2, respectively. To validate these BMI cut-offs for adiposity in the island population of Mauritius, we assessed the relationship between BMI and measured body fat mass in this population according to gender and ethnicity. METHODS: In 175 young adult Mauritians (age 20-42 years) belonging to the two main ethnic groups-Indians (South Asian descent) and Creoles (African/Malagasy descent), body weight, height and waist circumference (WC) were measured, total body fat assessed by deuterium oxide (D2O) dilution and trunk (abdominal) fat by segmental bioimpedance analysis. RESULTS: Compared to body fat% predicted from BMI using Caucasian-based equations, body fat% assessed by D2O dilution in Mauritians was higher by 3-5 units in Indian men and women as well as in Creole women, but not in Creole men. This gender-specific ethnic difference in body composition between Indians and Creoles is reflected in their BMI-Fat% relationships, as well as in their WC-Trunk Fat% relationships. Overall, WHO BMI cut-offs of 25 and 30 kg m-2 for overweight and obesity, respectively, seem valid only for Creole men (~24 and 29.5, respectively), but not for Creole women whose BMI cut-offs are 2-4 units lower (21-22 for overweight; 27-28 for obese) nor for Indian men and women whose BMI cut-offs are 3-4 units lower (21-22 for overweight; 26-27 for obese). CONCLUSIONS: The use of BMI cut-off points for classifying overweight and obesity need to take into account both ethnicity and gender to avoid gross adiposity status misclassification in this population known to be at high risk for type-2 diabetes and cardiovascular diseases. This is particularly of importance in obesity prevention strategies both in clinical medicine and public health.

Water-induced thermogenesis and fat oxidation: a reassessment.

BACKGROUND/OBJECTIVES: Drinking large amounts of water is often recommended for weight control. Whether water intake stimulates energy and fat metabolism is, however, controversial with some studies reporting that drinking half a litre or more of water increases resting energy expenditure (REE) by 10-30% and decreases respiratory quotient (RQ), whereas others report no significant changes in REE or RQ. The aim here was to reassess the concept of water-induced thermogenesis and fat oxidation in humans, with particular focus on interindividual variability in REE and RQ responses, comparison with a time-control Sham drink, and on the potential impact of gender, body composition and abdominal adiposity. SUBJECTS/METHODS: REE and RQ were measured in healthy young adults (n=27; body mass index range: 18.5-33.9 kg m(-2)), by ventilated hood indirect calorimetry for at least 30 min before and 130 min after ingesting 500 ml of purified (distilled) water at 21-22 °C or after Sham drinking, in a randomized cross-over design. Body composition and abdominal fat were assessed by bioimpedance techniques. RESULTS: Drinking 500 ml of distilled water led to marginal increases in REE (<3% above baseline), independently of gender, but which were not significantly different from Sham drinking. RQ was found to fall after the water drink, independently of gender, but it also diminished to a similar extent in response to sham drinking. Interindividual variability in REE and RQ responses was not associated with body fatness, central adiposity or fat-free mass. CONCLUSIONS: This study conducted in young men and women varying widely in adiposity, comparing the ingestion of distilled water to Sham drinking, suggests that ingestion of purified water per se does not result in the stimulation of thermogenesis or fat oxidation.

Pathways from dieting to weight regain, to obesity and to the metabolic syndrome: an overview.

Every year, scores of millions of people - as diverse as obese and lean, teenagers and older adults, sedentary and elite athletes, commoners and celebrities - attempt to lose weight on some form of diet. They are often encouraged by their parents, friends, health professionals, training coaches, a media that promotes a slim image and a diet-industry that in Europe and United States alone has an annual turnover in excess of $150 billion. Weight regain is generally the rule, with one-third to two-thirds of the weight lost being regained within 1 year and almost all is regained within 5 years. With studies of the long-term outcomes showing that at least one-third of dieters regain more weight than they lost, together with prospective studies indicating that dieting during childhood and adolescence predicts future weight gain and obesity, there is concern as to whether dieting may paradoxically be promoting exactly the opposite of what it is intended to achieve. Does dieting really make people fatter? How? Does dieting increase the risks for cardiometabolic diseases as many go through repeated cycles of intentional weight loss and unintentional weight regain, i.e. through yo-yo dieting or weight cycling? What's new in adipose tissue biology pertaining to the mechanisms that drive weight regain? Why does exercise not necessarily work in concert with dieting to achieve weight loss and prevent weight regain? What 'lessons' are we learning from bariatric surgery about the mechanisms by which long-term weight loss seems achievable? It is these questions, against a background of preoccupation with dieting, that recent advances and controversies relevant to the theme of 'Pathways from dieting to weight regain, to obesity and to the metabolic syndrome' are addressed in this overview and the eight review articles in this supplement reporting the proceedings of the 7th Fribourg Obesity Research Conference.

Dieting and weight cycling as risk factors for cardiometabolic diseases: who is really at risk?

Despite the poor prognosis of dieting in obesity management, which often results in repeated attempts at weight loss and hence weight cycling, the prevalence of dieting has increased continuously in the past decades in parallel to the steadily increasing prevalence of obesity. However, dieting and weight cycling are not limited to those who are obese or overweight as substantial proportions of the various population groups with normal body weight also attempt to lose weight. These include young and older adults as well as children and adolescents who perceive themselves as too fat (due to media, parental and social pressures), athletes in weight-sensitive competitive sports (i.e. mandatory weight categories, gravitational and aesthetic sports) or among performers for whom a slim image is professionally an advantage. Of particular concern is the emergence of evidence that some of the potentially negative health consequences of repeated dieting and weight cycling are more readily seen in people of normal body weight rather than in those who are overweight or obese. In particular, several metabolic and cardiovascular risk factors associated with weight cycling in normal-weight individuals have been identified from cross-sectional and prospective studies as well as from studies of experimentally induced weight cycling. In addition, findings from studies of experimental weight cycling have reinforced the notion that fluctuations of cardiovascular risk variables (such as blood pressure, heart rate, sympathetic activity, blood glucose, lipids and insulin) with probable repeated overshoots above normal values during periods of weight regain put an additional stress on the cardiovascular system. As the prevalence of diet-induced weight cycling is increasing due to the opposing forces of an 'obesigenic' environment and the media pressure for a slim figure (that even targets children), dieting and weight cycling is likely to become an increasingly serious public health issue.

How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery.

Whether dieting makes people fatter has been a subject of considerable controversy over the past 30 years. More recent analysis of several prospective studies suggest, however, that it is dieting to lose weight in people who are in the healthy normal range of body weight, rather than in those who are overweight or obese, that most strongly and consistently predict future weight gain. This paper analyses the ongoing arguments in the debate about whether repeated dieting to lose weight in normal-weight people represents unsuccessful attempts to counter genetic and familial predispositions to obesity, a psychosocial reaction to the fear of fatness or that dieting per se confers risks for fatness and hence a contributing factor to the obesity epidemic. In addressing the biological plausibility that dieting predisposes the lean (rather than the overweight or obese) to regaining more body fat than what had been lost (i.e. fat overshooting), it integrates the results derived from the re-analysis of body composition data on fat mass and fat-free mass (FFM) losses and recoveries from human studies of experimental energy restriction and refeeding. These suggest that feedback signals from the depletion of both fat mass (i.e. adipostats) and FFM (i.e. proteinstats) contribute to weight regain through the modulation of energy intake and adaptive thermogenesis, and that a faster rate of fat recovery relative to FFM recovery (i.e. preferential catch-up fat) is a central outcome of body composition autoregulation in lean individuals. Such a temporal desynchronization in the restoration of the body's fat vs. FFM results in a state of hyperphagia that persists beyond complete recovery of fat mass and interestingly until FFM is fully recovered. However, as this completion of FFM recovery is also accompanied by fat deposition, excess fat accumulates. In other words, fat overshooting is a prerequisite to allow complete recovery of FFM. This confers biological plausibility for post-dieting fat overshooting - which through repeated dieting and weight cycling would increase the risks for trajectories from leanness to fatness. Given the increasing prevalence of dieting in normal-weight female and male among young adults, adolescents and even children who perceive themselves as too fat (due to media, family and societal pressures), together with the high prevalence of dieting for optimizing performance among athletes in weight-sensitive sports, the notion that dieting and weight cycling may be predisposing a substantial proportion of the population to weight gain and obesity deserves greater scientific scrutiny.

Cardiovascular and metabolic responses to tap water ingestion in young humans: does the water temperature matter?

AIM: Drinking water induces short-term cardiovascular and metabolic changes. These effects are considered to be triggered by gastric distension and osmotic factors, but little is known about the influence of water temperature. METHODS: We determined, in a randomized crossover study, the acute cardiovascular and metabolic responses to 500 mL of tap water at 3 °C (cold), 22 °C (room) and 37 °C (body) in 12 young humans to ascertain an effect of water temperature. We measured continuous beat-to-beat haemodynamics, skin blood flux with laser-Doppler flowmetry and resting energy expenditure by indirect calorimetry starting with a 30-min baseline followed by a 4-min drink period and a subsequent 90-min post-drink observation. RESULTS: Ingestion of cold- and room-tempered water led to decreased heart rate (P < 0.01) and double product (P < 0.01), and increased stroke volume (P < 0.05); these effects were not observed with body-tempered water. Drinking cold- and room-, but not body-tempered water, led to increased high frequency power of heart rate variability (P < 0.05) and baroreflex sensitivity (P < 0.05). Cold- and room-tempered water increased energy expenditure over 90 min by 2.9% (P < 0.05) and 2.3% (ns), respectively, accompanied by a diminished skin blood flux (P < 0.01), thereby suggesting that both small increases in heat production together with decreased heat loss contribute to warming up the ingested water to intra-abdominal temperature levels. CONCLUSIONS: Overall, ingestion of cold- and room-, but not body-tempered water reduced the workload to the heart through a reduction in heart rate and double product which could be mediated by an augmented cardiac vagal tone.

Sitting comfortably versus lying down: is there really a difference in energy expenditure?

BACKGROUND & AIMS: Energy expenditure (EE) during sitting is widely assumed to be higher than that while lying down, but supporting evidence is equivocal. Despite this, resting EE in the sitting position is often used as a proxy for basal metabolic rate. Here we investigate whether EE differs in the comfortable seated position compared to supine (lying) position. METHODS: EE and respiratory quotient (RQ) were measured (by ventilated hood indirect calorimetry) in 19 healthy subjects (9 men, 10 women) after an overnight fast. Supine measurements were made using a comfortable clinical tilting table and sitting measurements made using an adjustable, ergonomic car seat adapted for the hood system. After about 30 min of rest in either position, metabolic monitoring was conducted until stabilization of EE for at least 15 min in each posture. RESULTS: EE in the sitting position was not significantly different compared to supine (<2% difference). By contrast, heart rate was higher by 7 beats/min (p < 0.05). RQ was slightly but significantly decreased during sitting compared to lying (p < 0.05), with no change in breathing rate. CONCLUSIONS: This study suggests that the ventilated hood calorimetry system for assessment of REE after an overnight fast in a comfortable sitting position can be used as a good proxy of the basal metabolic rate. It also underscores the applicability of the ventilated hood system to measurements of resting EE in the sitting posture which, compared to supine posture, may be more acceptable/convenient to the subject/patient participating in postprandial metabolic studies lasting several hours.

Body composition, inflammation and thermogenesis in pathways to obesity and the metabolic syndrome: an overview.

According to the World Health Organization, overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. What constitutes 'abnormal' fat accumulation in this definition is not specified, but this most likely represents a consensus term that encapsulates the importance of adipose tissue dysfunctions, rather than solely excess fat per se, in the pathogenesis of disease entities of the metabolic syndrome, particularly type 2 diabetes and cardiovascular diseases. Over the past decades, such abnormalities in fat accumulation have been linked to a pattern of fat distribution characterized by disproportionate fat deposition in the abdomen; to limits in the capacity of adipose tissue to expand resulting in the burden of fat storage being shifted to 'lean' tissues/organs as ectopic fat; and to the secretion (by both intrinsic and infiltrated cells within the adipose tissue mass) of a plethora of cytokines and other factors which via their autocrine, paracrine and/or endocrine actions underscore a state of chronic low-grade inflammation. These links have formed the basis of a multitude of adipocentric concepts that have stimulated basic and clinical research aimed at explaining differential susceptibilities to cardiometabolic diseases according to diet and lifestyle, birth weight and post-natal growth patterns, menopausal transition and the ageing process, race and ethnicity--often within the framework of hypotheses constructed around thrifty genotypes or thrifty phenotypes, and around overlapping molecular pathways implicated in metabolic inflammation, thermogenesis and body composition regulation. It is against this background of rapidly advancing research in metabolic health--fuelled as much by the search for early markers of cardiometabolic risks as by the search for 'druggable' molecular targets for treating obesity and its comorbidities--that fundamental concepts, controversies and novel research avenues relevant to the theme of 'Body composition, Inflammation and Thermogenesis in Pathways to Obesity and the Metabolic Syndrome' are addressed in this overview and the 10 review articles in this supplement reporting the proceedings of the 6th Fribourg Obesity Research Conference (FORC-2011).

Adaptive thermogenesis in human body weight regulation: more of a concept than a measurable entity?

According to Lavoisier, 'Life is combustion'. But to what extent humans adapt to changes in food intake through adaptive thermogenesis--by turning down the rate of heat production during energy deficit (so as to conserve energy) or turning it up during overnutrition (so as to dissipate excess calories)--has been one of the most controversial issues in nutritional sciences over the past 100 years. The debate nowadays is not whether adaptive thermogenesis exists or not, but rather about its quantitative importance in weight homoeostasis and its clinical relevance to the pathogenesis and management of obesity. Such uncertainties are likely to persist in the foreseeable future primarily because of limitations to unobtrusively measure changes in energy expenditure and body composition with high enough accuracy and precision, particularly when even small inter-individual variations in thermogenesis can, in dynamic systems and over the long term, be important in the determining weight maintenance in some and obesity and weight regain in others. This paper reviews the considerable body of evidence, albeit fragmentary, suggesting the existence of quantitatively important adaptive thermogenesis in several compartments of energy expenditure in response to altered food intake. It then discusses the various limitations that lead to over- or underestimations in its assessment, including definitional and semantics, technical and methodological, analytical and statistical. While the role of adaptive thermogenesis in human weight regulation is likely to remain more a concept than a strictly 'quantifiable' entity in the foreseeable future, the evolution of this concept continues to fuel exciting hypothesis-driven mechanistic research which contributes to advance knowledge in human metabolism and which is bound to result in improved strategies for the management of a healthy body weight.

Non-contact assessment of waist circumference: will tape measurements become progressively obsolete?

Waist circumference (WC) is a key variable to assess in health management as it is a proxy of abdominal fat mass and a surrogate marker of cardiometabolic disease risk, including the metabolic syndrome. Recently, a portable non-contact device calculating WC (ViScan) has been developed, which hence allows the tracking of WC independently of the inter-investigators error. We compared WC values obtained with this device with WC measured by simple non-stretchable tape in 74 adults of varying body mass indices (range 17-39 kg/m(2)). The correlation between the two methods was very high (r=0.97, P<0.0001) and the reproducibility (precision) assessed with a rigid phantom was excellent (<1 cm, coefficient of variability<1%). The instrument constitutes a potentially valuable tool for longitudinal surveys and comparative international studies, which require simple but precise measurements of WC in order to track the effect of subtle changes on various health outcomes.

Body composition phenotypes in pathways to obesity and the metabolic syndrome.

Dynamic changes in body weight have long been recognized as important indicators of risk for debilitating diseases. While weight loss or impaired growth can lead to muscle wastage, as well as to susceptibility to infections and organ dysfunctions, the development of excess fat predisposes to type 2 diabetes and cardiovascular diseases, with insulin resistance as a central feature of the disease entities of the metabolic syndrome. Although widely used as the phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI), that is, weight/height(2) (H(2)), which was developed as an operational definition for classifying both obesity and malnutrition, has considerable limitations in delineating fat mass (FM) from fat-free mass (FFM), in particular at the individual level. After an examination of these limitations within the constraints of the BMI-FM% relationship, this paper reviews recent advances in concepts about health risks related to body composition phenotypes, which center upon (i) the partitioning of BMI into an FM index (FM/H(2)) and an FFM index (FFM/H(2)), (ii) the partitioning of FFM into organ mass and skeletal muscle mass, (iii) the anatomical partitioning of FM into hazardous fat and protective fat and (iv) the interplay between adipose tissue expandability and ectopic fat deposition within or around organs/tissues that constitute the lean body mass. These concepts about body composition phenotypes and health risks are reviewed in the light of race/ethnic variability in metabolic susceptibility to obesity and the metabolic syndrome.

The time course of salt-induced hypertension, and why it matters.

The epidemiology of salt-induced hypertension has been explored in detail in animal studies, in some cases involving exposures to excess dietary salt for much of the animal's lifespan. The results of these studies demonstrate the presence of two distinct time courses of the blood pressure response to a high salt intake: an acute (rapid) blood pressure response occurring over days to weeks, and a slow and progressive blood pressure response that develops over extremely long periods of time, amounting to a significant fraction of the lifespan in normal individuals. The acute form of salt sensitivity is well known in humans, having often been demonstrated as a fall in blood pressure during the period of salt restriction. The slow and progressive form of salt sensitivity has been demonstrated directly in rats and chimpanzees and is also evident in analyses of human cross-population data as a salt dependency of age-associated changes of blood pressure. This slow and progressive component of salt-induced hypertension may be attributable, at least in part, to a progressive rise in the acute salt sensitivity of blood pressure during sustained exposure to high salt. However, a progressively irreversible or 'self sustaining' component of salt-induced hypertension has also been demonstrated in rat studies. This irreversible component has not been completely characterized, but its presence raises the possibility that blood pressure responses to salt restriction may not fully reveal the contribution of salt to blood pressure or the epidemiology of hypertension. These various components of salt sensitivity (acute vs slow, reversible vs irreversible) should be considered in any comprehensive explanation of the effects of salt on blood pressure and especially in experimental studies of the genetic and physiological mechanisms underlying salt-induced hypertension.

Sugary drinks in the pathogenesis of obesity and cardiovascular diseases.

Soft drink overconsumption is now considered to be a major public health concern with implications for cardiovascular diseases. This follows a number of studies performed in animals suggesting that chronic consumption of refined sugars can contribute to metabolic and cardiovascular dysregulation. In particular, the monosaccharide fructose has been attracting increasing attention as the more harmful sugar component in terms of weight gain and metabolic disturbances. High-fructose corn syrup is gradually replacing sucrose as the main sweetener in soft drinks and has been blamed as a potential contributor to the current high prevalence of obesity. There is also considerable evidence that fructose, rather than glucose, is the more damaging sugar component in terms of cardiovascular risk. This review focuses on the potential role of sugar drinks, particularly the fructose component, in the pathogenesis of obesity and cardiovascular diseases.