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Physical activity and obese children
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Journal of Sport and Health Science 1 (2012) 141e148 www.jshs.org.cn
Review
Physical activity and obese children Alison M. McManus*, Robin R. Mellecker Institute of Human Performance, University of Hong Kong, Hong Kong, China Received 23 June 2012; revised 31 August 2012; accepted 25 September 2012
Abstract Childhood obesity is an epidemic of global proportions, accompanied by an alarming increase in various metabolic disorders. It would appear that childhood obesity stems largely from excessive energy intake and that it is the ensuing obesity that leads to physical inactivity in children, as opposed to initial physical inactivity inducing obesity. How changes in body composition that accompany obesity influence physical activity (PA) and the mechanistic basis for this remains poorly understood. This review provides an overview of the PA habits and body composition of the obese children. We suggest skeletal muscle metabolism as a key driver of PA. The role both quantitative and qualitative changes in skeletal muscle may play in oxidative metabolism in the obese children are discussed. There is a real need for research examining the mechanistic basis of physical inactivity in the obese. The dearth of information on the role of skeletal muscle metabolism in the PA of obese youngsters and the emergence of new technologies allowing cellular and metabolite mechanisms to be explored provides plenty of scope for future work. Copyright Ó 2012, Shanghai University of Sport. Production and hosting by Elsevier B.V. All rights reserved. Keywords: Children; Exercise; Intervention; Obesity; Physical activity
1. Introduction Latest statistics from the World Health Organization indicate that between the years 1980 and 2008 worldwide obesity rates have doubled.1 While the country with the highest prevalence of overweight and obesity remains the USA, it is those countries which have undergone the most rapid economic development that have witnessed the most dramatic increases in obesity over this time-frame. Nowhere is this more acute than in China. The economy in China has grown at an annual average rate of 10% since 1990 and there has been a concomitant rise in levels of childhood obesity over this same timeframe. The high degree of regional specificity in obesity prevalence rates in China most * Corresponding author. E-mail address: [email protected] (A.M. McManus) Peer review under responsibility of Shanghai University of Sport
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aptly illustrates the parallel between economic development and obesity. Less developed, non-coastal and rural regions have maintained combined overweight and obesity levels corresponding with the countrywide value of less than 5% for the 1980s. In contrast, by 2005 the rapidly developed coastal and urbanized regions have seen childhood overweight and obesity climb to over 30% in boys and 15% in girls.2 The potential for physical activity (PA) to play a protective role against excessive adiposity has led to a plethora of research documenting the relationship between PA and excessive fat gain. PA is generally conceptualized as activity that is of at least moderate intensity (3 metabolic equivalent tasks (METs)).3,4 Describing a child as inactive indicates that the child is not performing sufficient (defined by specific PA guidelines) moderate to vigorous activity.3,4 Sedentary behavior on the other hand is waking behavior that requires very low levels of energy expenditure (1.5 METs).3,4 All tasks that require more energy than sedentary behaviors but are not at least moderate intensity are categorized as light activity.3,4 Strong inverse correlations between accelerometer determined PA and precise measures of body composition have been documented in children.5e7 These findings lend support to the
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belief that PA is important in the prevention of obesity. In contrast, a review of the available prospective study of objectively assessed PA and gains in adiposity has concluded that PA is a poor predictor of increases in excessive fatness.8 The crosssectional nature of many of the association studies has meant that there is the strong possibility of reverse causality, i.e., obesity leading to lower PA levels, as opposed to physical inactivity leading to obesity.9 When the energy flux, or the change over time in the balance between energy intake and energy expenditure, has been scrutinized, a positive relationship has been found between body weight and energy flux.10 This suggests that it is increases in total energy intake, as opposed to decreases in total energy expenditure, that are driving increases in body weight. Although there is still no consensus on which side of the energy balance equation is contributing the most to the imbalance, a recent meta-analysis provides substantial evidence that reverse causality may have hampered our interpretation of cross-sectional findings relating PA to adiposity.11 The results of the meta-analysis, which examined objectively measured PA and changes in body fatness over time, appear to support the premise that excessive fatness leads to inactivity in children, as opposed to inactivity inducing obesity. Given the public health significance of the increasing worldwide prevalence of obesity, the importance of establishing the causal relationship between obesity and PA cannot be overestimated. Understanding the potential influence of being obese on PA is therefore the focus of this review. The review begins with an overview of the PA habits of obese children. A discussion of how body composition varies in obesity follows. We then consider skeletal muscle metabolism as a key driver of PA and possible mechanisms underlying deficits in skeletal muscle metabolism in the obese children are proposed. The review concludes with consideration of the benefits and challenges associated with obese youngsters becoming physically active. An electronic search of the following databases was done within the maximum time periods available in their archives: PubMed Central (1946e2012), Medline (1973e2012), and Cochrane Library (1973e2012). Our common search terms were matched to the Medical Subject Headings (MeSH) index and included: Child, Adolescent, Physical activity, Obesity, Adiposity. We used combinations of these common search terms alongside each area of interest such as Muscles/skeletal/metabolism, Energy metabolism, Exercise/physiology, Pulmonary gas exchange, Kinetics, Genomics, Metabolomics/metabonomics, etc. This was supplemented with book chapters and journal article citation searches. Only English language publications which included children and adolescents aged 4e18 years old were included. 2. PA in obese childrena How active are obese children? Are they less active than their non-obese counterparts? It would seem that regardless of a
Because of the inherent limitations with self-reported PA, particularly in young people, only those studies which use an objective measure of PA will be considered.12,13
A.M. McManus and R.R. Mellecker
the measurement device, (accelerometry, heart rate measurement, or doubly-labeled water), the obese children generally exhibit lower levels of activity. For example, Maffeis and colleagues14 used heart rate monitoring to estimate PA in a small group of 8e10-year-old obese (body mass index (BMI) >97th percentile) and non-obese children. Non-obese children spent about 100 min a day more being physically active (all activity above sedentary behavior) than the obese children. Moderate to vigorous PA was similar in the two groups, so the difference in total daily activity was accounted for by light intensity activity. The authors also found that the obese children spent more time (approximately 100 min a day) engaged in sedentary pursuits compared to the non-obese children. These findings are similar to Yu et al.15 who also used heart rate derived estimates of energy expenditure to compare total activity (activity above sedentary behavior) and sedentary behavior between 18 obese (BMI 95th percentile) and 18 non-obese 6e18-year-olds. The obese youngsters in Yu et al.’s15 study spent 30% less of the monitored time engaged in physically active pursuits (no data are provided for the breakdown of light, moderate or vigorous activity), but 51% more time engaged in sedentary activities during the waking hours. Accelerometry studies also found lower PA levels in obese youngsters. In a group of 53 obese (BMI 98th percentile) and 53 non-obese boys and girls (mean age 8.6 years), Hughes and colleagues16 found total activity time (mean accelerometer counts/min) was lower in the obese (648 counts/min) compared to non-obese children (729 counts/ min). Interestingly there was no difference in time spent being sedentary between the two groups of children in this study. When the proportion of the time spent engaged in activities of moderate to vigorous intensity was compared this was marginally less (2.4%) in the obese (average of about 16 min a day) compared to the non-obese (average of about 23 min a day). Similarly, Page et al.17 found that time spent being moderately to vigorously active was slightly less in 14 obese (BMI >99th percentile; average of about 10 min a day) compared with 54 non-obese (average of about 13 min a day) 10-year-olds. Although total activity and PA are generally less in the obese children and adolescent compared to the non-obese, total activity energy expenditure is not always reduced. Ekelund et al.18 assessed total activity energy expenditure and PA using a combined doubly-labeled water and accelerometer approach in 18 obese (BMI >30 kg/m2) and 18 non-obese adolescents. They found no difference in total activity energy expenditure when adjusted for lean body mass, but lower levels of PA in the obese. These findings are concordant with others who have also found that when total energy expenditure is adjusted for size values are similar between the obese and non-obese.19e22 Ekelund et al.18 concluded that PA does not necessarily equate to the total energy cost of activity because of the often-overlooked low-intensity component of total activity energy expenditure. They suggested that low-tomoderate intensity activities determine overall PA level to a greater extent than vigorous activities. Low intensity PA is
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rarely reported, but may be an overlooked aspect of PA of obese children. Light intensity activity is acquired from the frequent, shortduration day-to-day activities, rather than sustained organized sport or exercise. The usual way of expressing PA, using summary measures such as total PA or total time spent in differing intensity categories such as moderate-to-vigorous PA, does not adequately capture the various dimensions of short-duration, sporadic PA, such as the frequency, duration and intensity of movement bouts, as well as the sedentary intervals between these. To the best of our knowledge, only one report provides detailed information of this kind for the obese children. McManus and colleagues23 monitored 42 obese (BMI >90th percentile) and 42 age- and sex-matched non-obese 7e9-year-olds using second-by-second triaxial accelerometry over a 3-week period. Similar to Ekelund et al.’s18 work, activity was generally low intensity, and accounted for 71% and 68% of the total weekday and weekend PA respectively in both the obese and non-obese. Whilst the length and intensity of activity bouts were similar in the obese and non-obese, the obese children experienced fewer activity bouts across the waking day, coupled with longer rest periods between bouts of movement, especially at the weekend. Work by Stone et al.24 comparing lean and overweight (BMI 85th percentile) boys, found that the number of short-duration light intensity bouts of movement in a day was very high, with more than 900 bouts per weekday of, on average, 11e12 s in duration in both lean and obese during the weekday or weekend. The obese children in the study of McManus et al.23 experienced significantly fewer short-duration low-intensity bouts (788 bouts/day, about 170 less bouts than the non-obese) during the weekday and substantially less (483 bouts/day, over 190 fewer bouts than the non-obese) at the weekend. In contrast, the overweight boys in Stone et al.’s24 study experienced a similar number of active bouts both during the week and at the weekend. Differences in these findings may reflect differing data processing approaches, as well as the differing environmental settings of the two studies. Alternatively, is it possible that more pronounced restrictions on PA may be a feature of more pronounced changes in body composition that accompany obesity, rather than a feature of being overweight?
3. What are the shifts in body composition that accompany obesity? Obesity is most commonly classified using BMI or by expressing fatness as a percentage of total mass. These single measures of body composition have been shown to be unsatisfactory because of the failure to account for changes in other components of body composition.25 For example, BMI does not account for relative leanness and at any given BMI there can be widely varying degrees of body fatness.26 Percentage body fat is problematic because without adjustment for size, this measure is also influenced by the relative leanness of the individual.25 Fat mass index (FMI; FMI ¼ fat mass (kg/m2) and fat-free mass index (FFMI; FFMI ¼ fat-free mass (kg/m2) have been proposed as superior measures for tracking changes in body composition during growth and development, and for investigating changes in body composition with increasing adiposity.26 These relative indices take into account the height of the individual, and allow a measure of the relative contribution of fat mass and fat-free mass for a given BMI.27 Values for both FMI and FFMI under the age of 11 years and between 11 and 18 years are provided in Table 1 for boys and girls of differing levels of adiposity. Both FMI and FFMI increase with age in girls.28e31 Obese girls show similar increases with age, but FMI is substantially greater, with FFMI marginally higher.30,31 In boys FMI remains relatively stable with increasing age, whilst FFMI increases with age.28e31 Again the change with age is similar in obese boys, but values for FMI are substantially higher, with FFMI marginally greater.30,31 For any given level of fatness, obese children may have differing levels of FFMI. Often greater relative fatness is accompanied by a greater FFMI (Table 1). There is however variation in FFMI for a given BMI, albeit less than the variation in FMI, and it is possible for the obese children to have a relatively low FFMI.26 Data from 1003 Israeli primary school children illustrate this, identifying a small subset of obese children who are characterized by being tall and possessing a low fat-free mass.32 Using FMI and FFMI, differing subtypes of obesity have been classified in adults as: (1) sarcopenic obesity (high FMI and low FFMI), (2) proportional obesity (high FMI and normal
Table 1 Fat mass index (FMI) and fat-free mass index (FFMI) in boys and girls of differing age, race and adiposity (kg/m2). FMI
FFMI
Boys <12 years Non-obese31 Caucasian Asian Black Obese30,31 Mixed race Chinese
Girls 12 years
<12 years
Boys 12 years
Girls
<12 years
12 years
<12 years
12 years
3.5 4.6 4.3
4.4 4.1 3.9
4.8 4.4 4.9
6.1 6.6 8.1
14.2 14.2 15.2
17.4 15.2 18.3
13.7 13.3 14.3
15.2 15.4 16.6
10.4 9.6
8.8 10.3
11.4 9.4
14.8 9.6
16.3 15.8
19.2 19.7
15.9 15.2
18.8 16.0
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FFMI), and (3) muscular obesity (high FMI and high FFMI). The functional implications of differing quantities of fat and fat-free mass for a given BMI are potentially substantial, yet there is a dearth of information characterizing changes in FMI and FFMI in sufficient detail in obese children. 4. Skeletal muscle metabolism in the obese children It is quite possible that alterations in PA in the obese children stem from adjustments in the metabolic response to movement, given changes in both the quantity and quality of muscle create disparities in muscle metabolism and differing patterns of substrate utilization. PA may also exert influence on cellular attributes of skeletal muscle, which in turn alters the metabolic response to movement. A discussion of key features of skeletal muscle metabolism in the obese children, as well as consideration of possible mechanisms underlying this response follows. Any transition in muscular work from rest to short duration bouts of movement requires a rapid adjustment in ATP synthesis in order to match ATP usage.33 This is met initially by the ATP-CP system and anaerobic glycolysis. If the activity remains low intensity, reliance on anaerobic glycolysis is fleeting and oxidative metabolism attends to ATP synthesis. If PA is performed at higher intensities, the contribution of anaerobic glycolysis becomes more significant. Pulmonary oxygen uptake (VO2) has traditionally been used as a marker of oxidative metabolism and it is generally assumed that VO2 is linearly related to work rate, and at a given intensity, VO2 remains constant.34 These assumptions are however, not strictly true. The pulmonary oxygen uptake kinetic response to exercise has fast (primary) and slow components, reflecting the efficiency of skeletal muscle oxidative metabolism, the relative degree of fatigue and affording an understanding of the interplay between cardiopulmonary and metabolic processes during PA and how these may be affected by conditions such as obesity.35 The pulmonary oxygen uptake kinetic response to low-tomoderate intensity exercise (i.e., intensity below the gas exchange threshold) has been described by three phases. Phase I begins as soon as the child transits from a period of rest to a bout of PA. First there is a delay, followed by a rapid rise in oxygen uptake. This first phase is also known as the cardiodynamic phase and reflects cardiovascular and pulmonary adaptations. Phase I is not dependent on VO2, rather it is largely a marker of the increase in pulmonary blood flow. Phase I is followed by an exponential increase in VO2 (phase II) that drives VO2 to steady state (phase III). Phase II kinetics are also known as the primary (fast) component and are described by a time constant revealing the time taken to achieve 63% of the change in oxygen uptake. The primary component provides a very close reflection (within about 10%) of the kinetics of oxygen uptake at the muscle. In phases I and II, when ATP re-synthesis cannot be fully supported by oxidative phosphorylation, the additional energy requirements are met from oxygen stores, PCr, and glycolysis. The oxygen equivalent of these energy sources is known as the oxygen deficit and the faster the time constant the smaller the oxygen deficit.35
A.M. McManus and R.R. Mellecker
During higher intensity PA, activity that is above the gas exchange threshold, a slow component manifests at phase III. During low to moderate intensity activity, there is no phase III slow component, with VO2 attaining steady-state at the end of phase II. In comparison, during more vigorous intensity activity above the gas exchange threshold VO2 continues to rise above what would have been steady-state and this reflects a loss of muscle efficiency and ensuing fatigue. Despite the pulmonary oxygen uptake kinetic response to PA providing an excellent marker of skeletal muscle metabolism, information is scarce for the obese youngster. Salvadego et al.36 studied the pulmonary oxygen uptake kinetic response to constant load exercise of varying intensities (40%, 60%, and 80% of estimated peak VO2) in 14 obese (BMI >97th percentile) and 13 non-obese adolescent boys. They found a slower primary component during low intensity (40% peak VO2) exercise in the obese boys, suggesting a greater oxygen deficit and therefore increased metabolic contribution from anaerobic glycolysis, lowering exercise tolerance. What are the implications of this for daily PA patterns? Essentially, making rapid and frequent transitions between sedentary activities and low to moderate intensity PA will be more fatiguing in the obese children. Therefore one would expect longer rest periods and fewer activity bouts, which corresponds to the findings of McManus and colleagues.23 In the same study, a slow component was apparent during heavy intensity (80% peak VO2) exercise in both the lean and obese boys.36 Although the relative amplitude of the slow component was similar between the two groups, the best fit for the pulmonary oxygen uptake kinetic response during the slow component was a linear function in the obese, and exponential function in the normal weight boys. A significant inverse relationship was reported for the slope of the linear increase in oxygen uptake and time to exhaustion during the slow component and lends supports to the proposition that during high-intensity PA obese children will experience greater levels of fatigue because they will attain maximum quicker. This may well account for the lower levels of moderate to vigorous PA noted in studies of free-living PA in obese youngsters.16,17 Caution in making such conclusions from the findings of this study are warranted however, given that the intensity of the constant load exercise bouts utilized corresponded to a percentage of peak oxygen uptake, rather than to individual gas exchange threshold values. This may have resulted in the obese children working at a higher relative workload, which appears to be the case at 60% of maximal oxygen uptake where nine of the 14 obese adolescents displayed a slow component, not apparent in any of the non obese adolescents. 5. Mechanism underlying deficits in skeletal muscle metabolism 5.1. Muscle fiber distribution and substrate utilization In human muscles there is substantial variability in fiber type proportions. Muscle fiber typing usually categorizes the many differing skeletal muscle fibers into three main groups
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(Type I, Type IIa, and Type IIb) according to their relative speed of contraction and metabolic properties. Type I or slow twitch fibers are smaller, slower to contract, and not capable of generating as much force as Type II fibers. Type I fibers are fatigue resistant; that is, they can continue to contract repeatedly without undue fatigue. They contain many mitochondria and are surrounded by several capillaries, ensuring a generous supply of oxygen and therefore have a high capacity for oxidative metabolism. Type IIa fibers exhibit characteristics of both Type I and Type IIb fibers. They resemble Type IIb fibers in that they are large, fast, capable of forceful contraction, and high in glycolytic capacity. They are also similar to Type I fibers because they have more mitochondria, a moderate capillary supply, and higher oxidative capacity compared with Type IIb fibers. Type IIb fibers are the largest, fastest, and most forceful of the three main fiber categories. They have a low oxidative capacity, but high anaerobic glycolytic capacity and are capable of producing large amounts of lactic acid, fatiguing easily. Studies have shown that the skeletal muscle of obese adults are comprised of a lower proportion of oxidative type I skeletal muscle fibers muscle.37,38 This would suggest oxidative metabolism is attenuated in the obese and this proposition is supported by evidence that obese adults show an impaired capacity to oxidize fats, which has been coupled to hastened weight gain.39 In children there has been no thorough investigation of the relationship between adiposity and skeletal muscle fiber type, largely because of ethical limitations of the muscle biopsy. There is evidence that the young child is an “oxidative specialist”, possessing few Type IIb skeletal muscle fibers and a predominance of Type I and Type IIa skeletal muscle fibers.40 The percentage distribution of type IIa and IIb skeletal muscle fibers attains adult values during late adolescence.38 Whether the developmental trajectory toward the adult skeletal muscle fiber distribution pattern differs in the obese children is not known. There is limited evidence of impaired exercise fat oxidation in the obese children. Zunquin et al.41 reported lower maximal exercise fat oxidation values for obese pubertal boys compared to the lean. Evidence is available that indicates deficits in fat oxidation can be reversed through targeted PA intervention, which may also augment positive alterations in body composition.42,43 It should be noted though, that these interventions have all been delivered in combination with dietary manipulation and it is therefore not possible to ascertain the respective influence of the PA intervention or the dietary manipulation. Unlike adults, impaired fat oxidation has not been shown to predict future development of obesity in childhood.44
capacity for fatty acid oxidation in skeletal muscle.45 These changes may be brought about simply by the changes in body composition associated with being obese, and are indeed more pronounced in the severely obese.45 Alternatively, they may be related to the combined effect of being obese and a lack of adequate muscular contraction. Skeletal muscle is a uniquely plastic tissue and PA induced muscular contractions create a host of intracellular changes that are believed to drive adaptive processes that improve metabolic efficiency and oxidative capacity. The skeletal muscle phenotype is therefore adaptable in response to PA. Adaptations include changes in mitochondrial numbers, as well as changes in molecular factors regulating skeletal muscle metabolism and examples of these follows. A recent study provides evidence that exercise creates transient changes in DNA methylation in adults.46 DNA methylation plays a key role in the control of gene expression and may help to explain the mechanism underlying various intracellular responses to muscular contraction, such as alterations in skeletal muscle nuclear receptors. A number of skeletal muscle nuclear receptors are associated with increased adiposity in both adults and children47 (e.g., peroxisome proliferator-activated receptors delta (PPAR-d) and gamma (PPAR-g)). These have also been found to be important regulators of oxidative metabolism in adults.48 Unfortunately we know little about the interaction between PA and these nuclear receptors in either obese or non-obese children. Complex diseases such as obesity undoubtedly have a genetic component. As a consequence of the global increase in the prevalence of obesity, a great deal of emphasis has been placed upon discovering specific gene locations or DNA sequences, which could predict an individual’s susceptibility for obesity.49 Of those identified, the fat mass and obesity gene FTO appears to have one of the largest effects on obesity and therefore is important for identifying obesity risk. The interaction between PA and this candidate gene is important in enhancing our understanding of how PA can modulate genetic contributions to obesity and recent work with adults shows that PA reduces the influence of particular variants of the FTO gene on BMI by up to 30%.50 Interestingly no interaction was found between variants of the FTO gene and PA in more than 19,000 child cases.50 These findings corroborate the weak relationship noted earlier between BMI and PA during childhood, but also reinforce the need for more detailed markers of body composition such as FFMI and FMI, in order to properly understand these relationships.
5.2. Cellular adjustments with physical inactivity and sedentary behavior
Although the evidence is not yet available in children, in adults there is clearly support for the hypothesis that obesity susceptibility lies not just within an individual gene, but within the interaction of the gene with other genes and with environmental variation such as PA. Changes in the concentration of metabolites (small molecules generated during metabolism) can provide a window into the interaction between genetic
One explanation for deficits in skeletal muscle oxidative metabolism in the obese is that shifts in intracellular processes occur such as reductions in key enzymes associated with the oxidation of fats such as citrate synthase, thus reducing the
5.3. Circulating metabolites, obesity, and PA
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variation and PA, and although we have known this for many decades, limitations in technology has meant we have relied upon traditional biomarker techniques of macro-metabolites such as glucose or blood lactate. Whilst valuable, these traditional biomarkers are isolated techniques using preselected macro-metabolites. As such a comprehensive understanding of the relationships between PA, metabolite composition and obesity in children is not currently available. The development of metabolic profiling using metabonomics is providing a powerful way of examining the metabolic basis of both obesity and PA and may reveal potential markers for mechanisms underlying muscle bioenergetics. Metabonomics provides a global analysis of multiple metabolites and the identification of patterns of circulating molecules that discriminate one group from another on the basis of particular characteristics, for example, relative adiposity or muscularity, or specific aspects of PA or sedentary behavior.51 For example, metabonomic exploration of 163 circulating metabolites identified 12 circulating molecules that differentiated obese and lean adults.52 These differences were independent of PA and included marked increases in glycine and glutamine in the obese, suggesting these are a direct outcome of alterations in body composition. Serum proteins and metabolites exhibit considerable variance due to the effect of PA. These metabolic perturbations are not detected with sufficient sensitivity using conventional measures of macro-metabolites such as triglyceride or glucose, but can be sensitively detected utilizing metabonomics. For instance, the effect of strenuous exercise on 420 circulating molecules has been explored in young men. Thirty-four metabolites were identified as possible biomarkers of strenuous exercise, specifically glycerol and asparagine.53 Exploiting metabonomics in the younger population will be of enormous value both to furthering our understanding of the metabolic responses to PA in lean and obese and to expanding our ability to understand the physiology underlying these. 6. Becoming physically active Although the mechanisms underlying reductions in PA are not well understood in the obese children, there are numerous studies documenting the health benefits of becoming physically active. Health benefits are wide-ranging from improvements in lipid and glucose metabolic profiles and insulin resistance,54 to improved endothelial function55 and augmented respiratory function.56 Health outcomes such as these have usually occurred independent of changes in BMI. PA intervention has been shown to result in reductions in adiposity;57,58 however, caution is warranted in interpreting outcomes given many are related to reductions in BMI. It may be time for the focus to be shifted away from BMI as a marker of intervention success, and attention paid to the interplay between health related outcomes and alterations in quantitative aspects of muscle, muscle metabolism and muscle signaling. Whilst there are numerous potential health benefits arising from being physically active, getting obese youngsters to
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become active remains a challenge. The lack of success of many interventions illustrates just how difficult it is to create an intervention strategy that is of sustained interest to the pediatric population.59 Much of the previous intervention work with obese youngsters has relied on an adult evidencebase and although short-term success is regularly apparent, longer-term adherence has been limited.60,61 Consideration of the differences in the obese children’s physiology and their PA patterns have been largely ignored, but in order to successfully deliver PA programmes to obese young people these require attention. 7. Summary Our current understanding of the influence obesity has upon PA in children is primitive and lacks mechanistic explanation. In this review we have proposed that being obese results in changes to skeletal muscle that create a cascade of cellular metabolic alterations, impacting upon the obese children’s ability to be physically active. Whether these changes occur solely because of shifts in body composition in the obese, or whether the disruptions noted in skeletal muscle metabolism occur because of the combined influence of shifts in body composition and inadequate PA is, to date, unknown. Establishing the causal relationship between obesity and physical inactivity is imperative for curbing the obesity epidemic and will require extending our knowledge of how body composition changes with obesity in the child, and how these changes impact upon PA. Importantly, it will require examination of the mechanistic basis of PA in the obese. The dearth of information on the role skeletal muscle metabolism may play in obesity and the emergence of new technologies allowing cellular and metabolite mechanisms to be explored provides plenty of scope for future work. References 1. World Health Organisation. World health statistics 2012. Available at: http:// www.who.int/gho/publications/world_health_statistics/2012/en/ [accessed 16.05.12]. 2. Cheng YJ, Tsung OC. Epidemic increase in overweight and obesity in Chinese children from 1985 to 2005. Int J Cardiol 2009;132:1e10. 3. Tremblay MS, Colley RC, Saunders TJ, Healy GN, Owen N. Physiological and health implications of a sedentary lifestyle. Appl Physiol Nutr Metab 2010;35:725e40. 4. Sedentary Behaviour Research Network. Letter to the editor: standardized use of the terms “sedentary” and “sedentary behaviours”. Appl Physiol Nutr Metab 2012;37:540e2. 5. Dencker M, Thorsson O, Karlsson MK, Linde´n C, Eiberg S, Wollmer P, et al. Daily physical activity related to body fat in children aged 8e11 years. J Pediatr 2006;149:38e42. 6. Ness AR, Leary SD, Mattocks C, Blair SN, Reilly JJ, Wells J, et al. Objectively measured physical activity and fat mass in a large cohort of children. PLoS Med 2007;4:e97. 7. Jimenez-Pavon D, Kelly J, Reilly JJ. Associations between objectively measured habitual physical activity and adiposity in children and adolescents: systematic review. Int J Pediatr Obes 2010;5:3e18. 8. Wilks DC, Besson H, Lindroos AK, Ekelund U. Objectively measured Physical activity and obesity prevention in children, adolescents and adults: a systematic review of prospective studies. Obes Rev 2010;12:e119e29.
Physical activity in obese children 9. Metcalf BS, Hosking J, Jeffery AN, Voss LD, Henley W, Wilkin TJ. Fatness leads to inactivity, but inactivity does not lead to fatness: a longitudinal study in children (EarlyBird 45). Arch Dis Child 2011;96:942e7. 10. Swinburn BA, Sacks G, Lo SK, Westerterp KR, Rush EC, Rosenbaum M, et al. Estimating the changes in energy flux that characterize the rise in obesity prevalence. Am J Clin Nutr 2009;89:1723e8. 11. Wilks DC, Sharp SJ, Ekelund U, Thompson SG, Mander AP, Turner RM, et al. Objectively measured physical activity and fat mass in children: a bias-adjusted meta-analysis of prospective studies. PLoS ONE 2011;6:e17205. 12. Ekelund U, Tomkinson GR, Armstrong N. What proportion of youth are physically active? Measurement issues, levels and recent time trends. Br J Sports Med 2011;45:859e65. 13. Colbert LH, Schoeller DA. Expending our physical activity (measurement) budget wisely. J Appl Physiol 2011;111:606e7. 14. Maffeis C, Zaffanello M, Pinelli L, Schutz Y. Total energy expenditure and patterns of activity in 8e10-year-old obese and nonobese children. J Pediatr Gastroenterol Nutr 1996;23:256e61. 15. Yu CW, Sung RYT, So R, Lam K, Nelson EAS, Li AM, et al. Energy expenditure and physical activity of obese children: cross-sectional study. Hong Kong Med J 2002;8:313e7. 16. Hughes AR, Henderson A, Ortiz-Rodriguez V, Artinou ML, Reilly JJ. Habitual physical activity and sedentary behaviour in a clinical sample of obese children. Int J Obes 2006;30:1494e500. 17. Page A, Cooper AR, Stamatakis E, Foster LJ, Crowne EC, Sabin M, et al. Physical activity patterns in nonobese and obese children assessed using minute-by-minute accelerometry. Int J Obes 2005;29:1070e6. 18. Ekelund U, Aman J, Yngve A, Renman C, Westerterp K, Sjo¨stro¨m M. Physical activity but not energy expenditure is reduced in obese adolescents: a case-control study. Am J Clin Nutr 2002;76:935e41. 19. Salbe AD, Fontvieille AM, Harper IT, Ravussin E. Low levels of physical activity in 5-year-old children. J Pediatr 1997;131:423e9. 20. Treuth MS, Figueroa-Colon R, Hunter GR, Weinsier RL, Butte NF, Goran MI. Energy expenditure and physical fitness in overweight vs. nonoverweight prepubertal girls. Int J Obes Relat Metab Disord 1998;22:440e7. 21. Bandini LG, Schoeller DA, Dietz WH. Energy expenditure in obese and nonobese adolescents. Pediatr Res 1990;27:198e203. 22. Maffeis C, Schutz Y, Schena F, Zaffanello M, Pinelli L. Energy expenditure during walking and running in obese and nonobese prepubertal children. J Pediatr 1993;123:193e9. 23. McManus AM, Chu EYW, Yu CCW, Hu Y. How children move: activity pattern characteristics in lean and obese Chinese children. J Obes 2011;2011:679328. 24. Stone MR, Rowlands AV, Eston RG. Characteristics of the activity pattern in normal weight and overweight boys. Prev Med 2009;49:205e8. 25. Wells JCK. Body composition in childhood: effects of normal growth and disease. Proc Nutr Soc 2003;62:521e8. 26. Wells JCK. A Hattori chart analysis of body mass index in infants and children. Int J Obes 2000;24:325e9. 27. Van Itallie TB, Yang M, Heymsfield SB, Funk RC, Boileau RA. Heightnormalised indices of the body’s fat-free and fat mass: potentially useful indicators of nutritional status. Am J Clin Nutr 1990;52:953e9. 28. Eissa MA, Dai S, Mihalopoulos NL, Day RS, Harrist RB, Labarthe DR. Trajectories of fat mass index, fat free-mass index, and waist circumference in children Project HeartBeat! Am J Prev Med 2009;37(Suppl. 1):S34e9. 29. Nakao T, Komiya S. Reference norms for a fat-free mass index and fat mass index in the Japanese child population. J Physiol Anthropol Appl Hum Sci 2003;22:293e8. 30. Ma J, Feng N, Zhang SW, Pan YP, Huang YB. Comparison of changes in body composition during puberty development of obese and normalweight children in China. Biomed Environ Sci 2009;22:413e8. 31. Freedman DS, Wang J, Maynard LM, Thornton JC, Meil Z, Pierson RN, et al. Relation of BMI to fat and fat-free mass among children and adolescents. Int J Obes 2005;29:1e8. 32. Ralt D. Low muscle mass-tall and obese children a special genre of obesity. Med Hypotheses 2007;68:750e5. 33. Armstrong N, McManus AM. Physiology of elite young male athletes. Med Sport Sci 2011;56:1e22.
147 34. Astrand PO, Rodahl K, Dahl H, Strømme SB. Textbook of work physiology: physiological bases of exercise. 4th ed. Champaign, IL: Human Kinetics; 2003. 35. Armstrong N, Barker AR. Oxygen uptake kinetics in children and adolescents: a review. Pediatr Exerc Sci 2009;21:130e47. 36. Salvadego D, Lazzer S, Busti C, Galli R, Agosti F, Lafortuna C, et al. Gas exchange kinetics in obese adolescents. Inferences on exercise tolerance and prescription. Am J Physiol Regul Integr Comp Physiol 2010;299:R1298e305. 37. Tanner CJ, Barakat HA, Dohm GL, Pories WJ, MacDonald KG, Cunningham PR, et al. Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metab 2002;282:E1191e6. 38. Hickey MS, Carey JO, Azevedo JL, Houmard JA, Pories WJ, Israel RG, et al. Skeletal muscle fiber composition is related to adiposity and in vitro glucose transport rate in humans. Am J Physiol 1995;268(3 Pt 1):E453e7. 39. Zurlo F, Lillioja S, Esposito-Del Puente A, Nyomba BL, Raz I, Saad MF, et al. Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. Am J Physiol 1990;259:E650e7. 40. Kriketos AD, Baur LA, O’Connor J, Carey D, King S, Caterson ID, et al. Muscle fibre type composition in infant and adult populations and relationships with obesity. Int J Obes 1997;21:796e801. 41. Zunquin G, Theunynck D, Sesboue B, Arhan P, Bougle D. Comparison of fat oxidation during exercise in lean and obese pubertal boys: clinical implications. Br J Sports Med 2009;43:869e70. 42. Ben Ounis O, Elloumi M, Zouhal H, Makni E, Denguezli M, Amri M, et al. Effect of individualized exercise training combined with diet restriction on inflammatory markers and IGF-1/IGFBP-3 in obese children. Ann Nutr Metab 2010;56:260e6. 43. Ben Ounis O, Elloumi M, Zouhal H, Makni E, Lac G, Tabka Z, et al. Effect of an individualized physical training program on resting cortisol and growth hormone levels and fat oxidation during exercise in obese children. Ann Endocrinol (Paris) 2011;72:34e41. 44. Salbe AD, Weyer C, Harper I, Lindsay RS, Ravussin E, Tataranni A. Assessing risk factors for obesity between childhood and adolescence: II. energy metabolism and physical activity. Pediatrics 2002;110:307e14. 45. Houmard JA, Pories WJ, Dohm GL. Severe obesity: evidence for a deranged metabolic program in skeletal muscle? Exerc Sport Sci Rev 2012;40:204e10. 46. Barres R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 2012;15:405e11. 47. Lagou V, Scott RA, Manios Y, Chen TL, Wang G, Grammatikaki E, et al. Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS study. Obesity 2008;16:913e8. 48. Ehrenborg E, Krook A. Regulation of skeletal muscle physiology and metabolism by peroxisome proliferator-activated receptor delta. Pharmacol Rev 2009;61:373e93. 49. Speakman JR, O’Rahilly S. Fat: an evolving issue. Dis Model Mech 2012;5:569e73. 50. Kilpelainen TO, Qi L, Brage S, Sharp SJ, Sonestedt E, Demerath E, et al. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med 2011;8:e1001116. 51. Ala-Korpela M. Potential role of body fluid 1H NMR metabonomics as a prognostic and diagnostic tool. Expert Rev Mol Diagn 2007;7:761e73. 52. Oberbach A, Bluher M, Wirth H, Till H, Kovacs P, Kullnick Y, et al. Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes. J Proteome Res 2011;10:4769e88. 53. Pohjanen E, Thysell E, Jonsson P, Eklund C, Silfver A, Carlsson IB, et al. A multivariate screening strategy for investigating metabolic effects of strenuous physical exercise in human serum. J Proteome Res 2007;6:2113e20. 54. Chang C, Liu W, Zhao X, Li S, Yu C. Effect of supervised exercise intervention on metabolic risk factors and physical fitness in Chinese obese children in early puberty. Obes Rev 2008;9(Suppl. 1):135e41.
148 55. Watts K, Beye P, Siafarikas A, Davis EA, Jones TW, O’Driscoll G, et al. Exercise training normalizes vascular dysfunction and improves central adiposity in obese adolescents. J Am Coll Cardiol 2004;43:1823e7. 56. Azad A, Gharakhanlou R, Niknam A, Ghanbari A. Effects of aerobic exercise on lung function in overweight and obese students. Tanaffos 2001;10:24e31. 57. Barbeau P, Johnson M, Howe C, Allison J, Davis C, Gutin B, et al. Ten months of exercise improves general and visceral adiposity, bone, and fitness in black girls. Obesity 2007;15:2077e85. 58. Kim Y, Lee S. Physical activity and abdominal obesity in youth. Appl Physiol Nutr Metab 2009;34:571e81.
A.M. McManus and R.R. Mellecker 59. van Sluijs E, McMinn A, Griffin S. Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials. BMJ 2008;42:653e7. 60. Summerbell C, Waters E, Edmunds L, Kelly S, Brown T, Campbell KJ. Interventions for preventing obesity in children. Cochrane Database Syst Rev 2005. http://dx.doi.org/10.1002/ 14651858.CD001871.pub2. 61. Waters E, de Silva-Sanigorski A, Hall BJ, Brown T, Campbell KJ, Gao Y, et al. Interventions for preventing obesity in children. Cochrane Database Syst Rev 2011. http://dx.doi.org/10.1002/14651858.CD001871.pub3.
Journal of Sport and Health Science 1 (2012) 141e148 www.jshs.org.cn
Review
Physical activity and obese children Alison M. McManus*, Robin R. Mellecker Institute of Human Performance, University of Hong Kong, Hong Kong, China Received 23 June 2012; revised 31 August 2012; accepted 25 September 2012
Abstract Childhood obesity is an epidemic of global proportions, accompanied by an alarming increase in various metabolic disorders. It would appear that childhood obesity stems largely from excessive energy intake and that it is the ensuing obesity that leads to physical inactivity in children, as opposed to initial physical inactivity inducing obesity. How changes in body composition that accompany obesity influence physical activity (PA) and the mechanistic basis for this remains poorly understood. This review provides an overview of the PA habits and body composition of the obese children. We suggest skeletal muscle metabolism as a key driver of PA. The role both quantitative and qualitative changes in skeletal muscle may play in oxidative metabolism in the obese children are discussed. There is a real need for research examining the mechanistic basis of physical inactivity in the obese. The dearth of information on the role of skeletal muscle metabolism in the PA of obese youngsters and the emergence of new technologies allowing cellular and metabolite mechanisms to be explored provides plenty of scope for future work. Copyright Ó 2012, Shanghai University of Sport. Production and hosting by Elsevier B.V. All rights reserved. Keywords: Children; Exercise; Intervention; Obesity; Physical activity
1. Introduction Latest statistics from the World Health Organization indicate that between the years 1980 and 2008 worldwide obesity rates have doubled.1 While the country with the highest prevalence of overweight and obesity remains the USA, it is those countries which have undergone the most rapid economic development that have witnessed the most dramatic increases in obesity over this time-frame. Nowhere is this more acute than in China. The economy in China has grown at an annual average rate of 10% since 1990 and there has been a concomitant rise in levels of childhood obesity over this same timeframe. The high degree of regional specificity in obesity prevalence rates in China most * Corresponding author. E-mail address: [email protected] (A.M. McManus) Peer review under responsibility of Shanghai University of Sport
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aptly illustrates the parallel between economic development and obesity. Less developed, non-coastal and rural regions have maintained combined overweight and obesity levels corresponding with the countrywide value of less than 5% for the 1980s. In contrast, by 2005 the rapidly developed coastal and urbanized regions have seen childhood overweight and obesity climb to over 30% in boys and 15% in girls.2 The potential for physical activity (PA) to play a protective role against excessive adiposity has led to a plethora of research documenting the relationship between PA and excessive fat gain. PA is generally conceptualized as activity that is of at least moderate intensity (3 metabolic equivalent tasks (METs)).3,4 Describing a child as inactive indicates that the child is not performing sufficient (defined by specific PA guidelines) moderate to vigorous activity.3,4 Sedentary behavior on the other hand is waking behavior that requires very low levels of energy expenditure (1.5 METs).3,4 All tasks that require more energy than sedentary behaviors but are not at least moderate intensity are categorized as light activity.3,4 Strong inverse correlations between accelerometer determined PA and precise measures of body composition have been documented in children.5e7 These findings lend support to the
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belief that PA is important in the prevention of obesity. In contrast, a review of the available prospective study of objectively assessed PA and gains in adiposity has concluded that PA is a poor predictor of increases in excessive fatness.8 The crosssectional nature of many of the association studies has meant that there is the strong possibility of reverse causality, i.e., obesity leading to lower PA levels, as opposed to physical inactivity leading to obesity.9 When the energy flux, or the change over time in the balance between energy intake and energy expenditure, has been scrutinized, a positive relationship has been found between body weight and energy flux.10 This suggests that it is increases in total energy intake, as opposed to decreases in total energy expenditure, that are driving increases in body weight. Although there is still no consensus on which side of the energy balance equation is contributing the most to the imbalance, a recent meta-analysis provides substantial evidence that reverse causality may have hampered our interpretation of cross-sectional findings relating PA to adiposity.11 The results of the meta-analysis, which examined objectively measured PA and changes in body fatness over time, appear to support the premise that excessive fatness leads to inactivity in children, as opposed to inactivity inducing obesity. Given the public health significance of the increasing worldwide prevalence of obesity, the importance of establishing the causal relationship between obesity and PA cannot be overestimated. Understanding the potential influence of being obese on PA is therefore the focus of this review. The review begins with an overview of the PA habits of obese children. A discussion of how body composition varies in obesity follows. We then consider skeletal muscle metabolism as a key driver of PA and possible mechanisms underlying deficits in skeletal muscle metabolism in the obese children are proposed. The review concludes with consideration of the benefits and challenges associated with obese youngsters becoming physically active. An electronic search of the following databases was done within the maximum time periods available in their archives: PubMed Central (1946e2012), Medline (1973e2012), and Cochrane Library (1973e2012). Our common search terms were matched to the Medical Subject Headings (MeSH) index and included: Child, Adolescent, Physical activity, Obesity, Adiposity. We used combinations of these common search terms alongside each area of interest such as Muscles/skeletal/metabolism, Energy metabolism, Exercise/physiology, Pulmonary gas exchange, Kinetics, Genomics, Metabolomics/metabonomics, etc. This was supplemented with book chapters and journal article citation searches. Only English language publications which included children and adolescents aged 4e18 years old were included. 2. PA in obese childrena How active are obese children? Are they less active than their non-obese counterparts? It would seem that regardless of a
Because of the inherent limitations with self-reported PA, particularly in young people, only those studies which use an objective measure of PA will be considered.12,13
A.M. McManus and R.R. Mellecker
the measurement device, (accelerometry, heart rate measurement, or doubly-labeled water), the obese children generally exhibit lower levels of activity. For example, Maffeis and colleagues14 used heart rate monitoring to estimate PA in a small group of 8e10-year-old obese (body mass index (BMI) >97th percentile) and non-obese children. Non-obese children spent about 100 min a day more being physically active (all activity above sedentary behavior) than the obese children. Moderate to vigorous PA was similar in the two groups, so the difference in total daily activity was accounted for by light intensity activity. The authors also found that the obese children spent more time (approximately 100 min a day) engaged in sedentary pursuits compared to the non-obese children. These findings are similar to Yu et al.15 who also used heart rate derived estimates of energy expenditure to compare total activity (activity above sedentary behavior) and sedentary behavior between 18 obese (BMI 95th percentile) and 18 non-obese 6e18-year-olds. The obese youngsters in Yu et al.’s15 study spent 30% less of the monitored time engaged in physically active pursuits (no data are provided for the breakdown of light, moderate or vigorous activity), but 51% more time engaged in sedentary activities during the waking hours. Accelerometry studies also found lower PA levels in obese youngsters. In a group of 53 obese (BMI 98th percentile) and 53 non-obese boys and girls (mean age 8.6 years), Hughes and colleagues16 found total activity time (mean accelerometer counts/min) was lower in the obese (648 counts/min) compared to non-obese children (729 counts/ min). Interestingly there was no difference in time spent being sedentary between the two groups of children in this study. When the proportion of the time spent engaged in activities of moderate to vigorous intensity was compared this was marginally less (2.4%) in the obese (average of about 16 min a day) compared to the non-obese (average of about 23 min a day). Similarly, Page et al.17 found that time spent being moderately to vigorously active was slightly less in 14 obese (BMI >99th percentile; average of about 10 min a day) compared with 54 non-obese (average of about 13 min a day) 10-year-olds. Although total activity and PA are generally less in the obese children and adolescent compared to the non-obese, total activity energy expenditure is not always reduced. Ekelund et al.18 assessed total activity energy expenditure and PA using a combined doubly-labeled water and accelerometer approach in 18 obese (BMI >30 kg/m2) and 18 non-obese adolescents. They found no difference in total activity energy expenditure when adjusted for lean body mass, but lower levels of PA in the obese. These findings are concordant with others who have also found that when total energy expenditure is adjusted for size values are similar between the obese and non-obese.19e22 Ekelund et al.18 concluded that PA does not necessarily equate to the total energy cost of activity because of the often-overlooked low-intensity component of total activity energy expenditure. They suggested that low-tomoderate intensity activities determine overall PA level to a greater extent than vigorous activities. Low intensity PA is
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rarely reported, but may be an overlooked aspect of PA of obese children. Light intensity activity is acquired from the frequent, shortduration day-to-day activities, rather than sustained organized sport or exercise. The usual way of expressing PA, using summary measures such as total PA or total time spent in differing intensity categories such as moderate-to-vigorous PA, does not adequately capture the various dimensions of short-duration, sporadic PA, such as the frequency, duration and intensity of movement bouts, as well as the sedentary intervals between these. To the best of our knowledge, only one report provides detailed information of this kind for the obese children. McManus and colleagues23 monitored 42 obese (BMI >90th percentile) and 42 age- and sex-matched non-obese 7e9-year-olds using second-by-second triaxial accelerometry over a 3-week period. Similar to Ekelund et al.’s18 work, activity was generally low intensity, and accounted for 71% and 68% of the total weekday and weekend PA respectively in both the obese and non-obese. Whilst the length and intensity of activity bouts were similar in the obese and non-obese, the obese children experienced fewer activity bouts across the waking day, coupled with longer rest periods between bouts of movement, especially at the weekend. Work by Stone et al.24 comparing lean and overweight (BMI 85th percentile) boys, found that the number of short-duration light intensity bouts of movement in a day was very high, with more than 900 bouts per weekday of, on average, 11e12 s in duration in both lean and obese during the weekday or weekend. The obese children in the study of McManus et al.23 experienced significantly fewer short-duration low-intensity bouts (788 bouts/day, about 170 less bouts than the non-obese) during the weekday and substantially less (483 bouts/day, over 190 fewer bouts than the non-obese) at the weekend. In contrast, the overweight boys in Stone et al.’s24 study experienced a similar number of active bouts both during the week and at the weekend. Differences in these findings may reflect differing data processing approaches, as well as the differing environmental settings of the two studies. Alternatively, is it possible that more pronounced restrictions on PA may be a feature of more pronounced changes in body composition that accompany obesity, rather than a feature of being overweight?
3. What are the shifts in body composition that accompany obesity? Obesity is most commonly classified using BMI or by expressing fatness as a percentage of total mass. These single measures of body composition have been shown to be unsatisfactory because of the failure to account for changes in other components of body composition.25 For example, BMI does not account for relative leanness and at any given BMI there can be widely varying degrees of body fatness.26 Percentage body fat is problematic because without adjustment for size, this measure is also influenced by the relative leanness of the individual.25 Fat mass index (FMI; FMI ¼ fat mass (kg/m2) and fat-free mass index (FFMI; FFMI ¼ fat-free mass (kg/m2) have been proposed as superior measures for tracking changes in body composition during growth and development, and for investigating changes in body composition with increasing adiposity.26 These relative indices take into account the height of the individual, and allow a measure of the relative contribution of fat mass and fat-free mass for a given BMI.27 Values for both FMI and FFMI under the age of 11 years and between 11 and 18 years are provided in Table 1 for boys and girls of differing levels of adiposity. Both FMI and FFMI increase with age in girls.28e31 Obese girls show similar increases with age, but FMI is substantially greater, with FFMI marginally higher.30,31 In boys FMI remains relatively stable with increasing age, whilst FFMI increases with age.28e31 Again the change with age is similar in obese boys, but values for FMI are substantially higher, with FFMI marginally greater.30,31 For any given level of fatness, obese children may have differing levels of FFMI. Often greater relative fatness is accompanied by a greater FFMI (Table 1). There is however variation in FFMI for a given BMI, albeit less than the variation in FMI, and it is possible for the obese children to have a relatively low FFMI.26 Data from 1003 Israeli primary school children illustrate this, identifying a small subset of obese children who are characterized by being tall and possessing a low fat-free mass.32 Using FMI and FFMI, differing subtypes of obesity have been classified in adults as: (1) sarcopenic obesity (high FMI and low FFMI), (2) proportional obesity (high FMI and normal
Table 1 Fat mass index (FMI) and fat-free mass index (FFMI) in boys and girls of differing age, race and adiposity (kg/m2). FMI
FFMI
Boys <12 years Non-obese31 Caucasian Asian Black Obese30,31 Mixed race Chinese
Girls 12 years
<12 years
Boys 12 years
Girls
<12 years
12 years
<12 years
12 years
3.5 4.6 4.3
4.4 4.1 3.9
4.8 4.4 4.9
6.1 6.6 8.1
14.2 14.2 15.2
17.4 15.2 18.3
13.7 13.3 14.3
15.2 15.4 16.6
10.4 9.6
8.8 10.3
11.4 9.4
14.8 9.6
16.3 15.8
19.2 19.7
15.9 15.2
18.8 16.0
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FFMI), and (3) muscular obesity (high FMI and high FFMI). The functional implications of differing quantities of fat and fat-free mass for a given BMI are potentially substantial, yet there is a dearth of information characterizing changes in FMI and FFMI in sufficient detail in obese children. 4. Skeletal muscle metabolism in the obese children It is quite possible that alterations in PA in the obese children stem from adjustments in the metabolic response to movement, given changes in both the quantity and quality of muscle create disparities in muscle metabolism and differing patterns of substrate utilization. PA may also exert influence on cellular attributes of skeletal muscle, which in turn alters the metabolic response to movement. A discussion of key features of skeletal muscle metabolism in the obese children, as well as consideration of possible mechanisms underlying this response follows. Any transition in muscular work from rest to short duration bouts of movement requires a rapid adjustment in ATP synthesis in order to match ATP usage.33 This is met initially by the ATP-CP system and anaerobic glycolysis. If the activity remains low intensity, reliance on anaerobic glycolysis is fleeting and oxidative metabolism attends to ATP synthesis. If PA is performed at higher intensities, the contribution of anaerobic glycolysis becomes more significant. Pulmonary oxygen uptake (VO2) has traditionally been used as a marker of oxidative metabolism and it is generally assumed that VO2 is linearly related to work rate, and at a given intensity, VO2 remains constant.34 These assumptions are however, not strictly true. The pulmonary oxygen uptake kinetic response to exercise has fast (primary) and slow components, reflecting the efficiency of skeletal muscle oxidative metabolism, the relative degree of fatigue and affording an understanding of the interplay between cardiopulmonary and metabolic processes during PA and how these may be affected by conditions such as obesity.35 The pulmonary oxygen uptake kinetic response to low-tomoderate intensity exercise (i.e., intensity below the gas exchange threshold) has been described by three phases. Phase I begins as soon as the child transits from a period of rest to a bout of PA. First there is a delay, followed by a rapid rise in oxygen uptake. This first phase is also known as the cardiodynamic phase and reflects cardiovascular and pulmonary adaptations. Phase I is not dependent on VO2, rather it is largely a marker of the increase in pulmonary blood flow. Phase I is followed by an exponential increase in VO2 (phase II) that drives VO2 to steady state (phase III). Phase II kinetics are also known as the primary (fast) component and are described by a time constant revealing the time taken to achieve 63% of the change in oxygen uptake. The primary component provides a very close reflection (within about 10%) of the kinetics of oxygen uptake at the muscle. In phases I and II, when ATP re-synthesis cannot be fully supported by oxidative phosphorylation, the additional energy requirements are met from oxygen stores, PCr, and glycolysis. The oxygen equivalent of these energy sources is known as the oxygen deficit and the faster the time constant the smaller the oxygen deficit.35
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During higher intensity PA, activity that is above the gas exchange threshold, a slow component manifests at phase III. During low to moderate intensity activity, there is no phase III slow component, with VO2 attaining steady-state at the end of phase II. In comparison, during more vigorous intensity activity above the gas exchange threshold VO2 continues to rise above what would have been steady-state and this reflects a loss of muscle efficiency and ensuing fatigue. Despite the pulmonary oxygen uptake kinetic response to PA providing an excellent marker of skeletal muscle metabolism, information is scarce for the obese youngster. Salvadego et al.36 studied the pulmonary oxygen uptake kinetic response to constant load exercise of varying intensities (40%, 60%, and 80% of estimated peak VO2) in 14 obese (BMI >97th percentile) and 13 non-obese adolescent boys. They found a slower primary component during low intensity (40% peak VO2) exercise in the obese boys, suggesting a greater oxygen deficit and therefore increased metabolic contribution from anaerobic glycolysis, lowering exercise tolerance. What are the implications of this for daily PA patterns? Essentially, making rapid and frequent transitions between sedentary activities and low to moderate intensity PA will be more fatiguing in the obese children. Therefore one would expect longer rest periods and fewer activity bouts, which corresponds to the findings of McManus and colleagues.23 In the same study, a slow component was apparent during heavy intensity (80% peak VO2) exercise in both the lean and obese boys.36 Although the relative amplitude of the slow component was similar between the two groups, the best fit for the pulmonary oxygen uptake kinetic response during the slow component was a linear function in the obese, and exponential function in the normal weight boys. A significant inverse relationship was reported for the slope of the linear increase in oxygen uptake and time to exhaustion during the slow component and lends supports to the proposition that during high-intensity PA obese children will experience greater levels of fatigue because they will attain maximum quicker. This may well account for the lower levels of moderate to vigorous PA noted in studies of free-living PA in obese youngsters.16,17 Caution in making such conclusions from the findings of this study are warranted however, given that the intensity of the constant load exercise bouts utilized corresponded to a percentage of peak oxygen uptake, rather than to individual gas exchange threshold values. This may have resulted in the obese children working at a higher relative workload, which appears to be the case at 60% of maximal oxygen uptake where nine of the 14 obese adolescents displayed a slow component, not apparent in any of the non obese adolescents. 5. Mechanism underlying deficits in skeletal muscle metabolism 5.1. Muscle fiber distribution and substrate utilization In human muscles there is substantial variability in fiber type proportions. Muscle fiber typing usually categorizes the many differing skeletal muscle fibers into three main groups
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(Type I, Type IIa, and Type IIb) according to their relative speed of contraction and metabolic properties. Type I or slow twitch fibers are smaller, slower to contract, and not capable of generating as much force as Type II fibers. Type I fibers are fatigue resistant; that is, they can continue to contract repeatedly without undue fatigue. They contain many mitochondria and are surrounded by several capillaries, ensuring a generous supply of oxygen and therefore have a high capacity for oxidative metabolism. Type IIa fibers exhibit characteristics of both Type I and Type IIb fibers. They resemble Type IIb fibers in that they are large, fast, capable of forceful contraction, and high in glycolytic capacity. They are also similar to Type I fibers because they have more mitochondria, a moderate capillary supply, and higher oxidative capacity compared with Type IIb fibers. Type IIb fibers are the largest, fastest, and most forceful of the three main fiber categories. They have a low oxidative capacity, but high anaerobic glycolytic capacity and are capable of producing large amounts of lactic acid, fatiguing easily. Studies have shown that the skeletal muscle of obese adults are comprised of a lower proportion of oxidative type I skeletal muscle fibers muscle.37,38 This would suggest oxidative metabolism is attenuated in the obese and this proposition is supported by evidence that obese adults show an impaired capacity to oxidize fats, which has been coupled to hastened weight gain.39 In children there has been no thorough investigation of the relationship between adiposity and skeletal muscle fiber type, largely because of ethical limitations of the muscle biopsy. There is evidence that the young child is an “oxidative specialist”, possessing few Type IIb skeletal muscle fibers and a predominance of Type I and Type IIa skeletal muscle fibers.40 The percentage distribution of type IIa and IIb skeletal muscle fibers attains adult values during late adolescence.38 Whether the developmental trajectory toward the adult skeletal muscle fiber distribution pattern differs in the obese children is not known. There is limited evidence of impaired exercise fat oxidation in the obese children. Zunquin et al.41 reported lower maximal exercise fat oxidation values for obese pubertal boys compared to the lean. Evidence is available that indicates deficits in fat oxidation can be reversed through targeted PA intervention, which may also augment positive alterations in body composition.42,43 It should be noted though, that these interventions have all been delivered in combination with dietary manipulation and it is therefore not possible to ascertain the respective influence of the PA intervention or the dietary manipulation. Unlike adults, impaired fat oxidation has not been shown to predict future development of obesity in childhood.44
capacity for fatty acid oxidation in skeletal muscle.45 These changes may be brought about simply by the changes in body composition associated with being obese, and are indeed more pronounced in the severely obese.45 Alternatively, they may be related to the combined effect of being obese and a lack of adequate muscular contraction. Skeletal muscle is a uniquely plastic tissue and PA induced muscular contractions create a host of intracellular changes that are believed to drive adaptive processes that improve metabolic efficiency and oxidative capacity. The skeletal muscle phenotype is therefore adaptable in response to PA. Adaptations include changes in mitochondrial numbers, as well as changes in molecular factors regulating skeletal muscle metabolism and examples of these follows. A recent study provides evidence that exercise creates transient changes in DNA methylation in adults.46 DNA methylation plays a key role in the control of gene expression and may help to explain the mechanism underlying various intracellular responses to muscular contraction, such as alterations in skeletal muscle nuclear receptors. A number of skeletal muscle nuclear receptors are associated with increased adiposity in both adults and children47 (e.g., peroxisome proliferator-activated receptors delta (PPAR-d) and gamma (PPAR-g)). These have also been found to be important regulators of oxidative metabolism in adults.48 Unfortunately we know little about the interaction between PA and these nuclear receptors in either obese or non-obese children. Complex diseases such as obesity undoubtedly have a genetic component. As a consequence of the global increase in the prevalence of obesity, a great deal of emphasis has been placed upon discovering specific gene locations or DNA sequences, which could predict an individual’s susceptibility for obesity.49 Of those identified, the fat mass and obesity gene FTO appears to have one of the largest effects on obesity and therefore is important for identifying obesity risk. The interaction between PA and this candidate gene is important in enhancing our understanding of how PA can modulate genetic contributions to obesity and recent work with adults shows that PA reduces the influence of particular variants of the FTO gene on BMI by up to 30%.50 Interestingly no interaction was found between variants of the FTO gene and PA in more than 19,000 child cases.50 These findings corroborate the weak relationship noted earlier between BMI and PA during childhood, but also reinforce the need for more detailed markers of body composition such as FFMI and FMI, in order to properly understand these relationships.
5.2. Cellular adjustments with physical inactivity and sedentary behavior
Although the evidence is not yet available in children, in adults there is clearly support for the hypothesis that obesity susceptibility lies not just within an individual gene, but within the interaction of the gene with other genes and with environmental variation such as PA. Changes in the concentration of metabolites (small molecules generated during metabolism) can provide a window into the interaction between genetic
One explanation for deficits in skeletal muscle oxidative metabolism in the obese is that shifts in intracellular processes occur such as reductions in key enzymes associated with the oxidation of fats such as citrate synthase, thus reducing the
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variation and PA, and although we have known this for many decades, limitations in technology has meant we have relied upon traditional biomarker techniques of macro-metabolites such as glucose or blood lactate. Whilst valuable, these traditional biomarkers are isolated techniques using preselected macro-metabolites. As such a comprehensive understanding of the relationships between PA, metabolite composition and obesity in children is not currently available. The development of metabolic profiling using metabonomics is providing a powerful way of examining the metabolic basis of both obesity and PA and may reveal potential markers for mechanisms underlying muscle bioenergetics. Metabonomics provides a global analysis of multiple metabolites and the identification of patterns of circulating molecules that discriminate one group from another on the basis of particular characteristics, for example, relative adiposity or muscularity, or specific aspects of PA or sedentary behavior.51 For example, metabonomic exploration of 163 circulating metabolites identified 12 circulating molecules that differentiated obese and lean adults.52 These differences were independent of PA and included marked increases in glycine and glutamine in the obese, suggesting these are a direct outcome of alterations in body composition. Serum proteins and metabolites exhibit considerable variance due to the effect of PA. These metabolic perturbations are not detected with sufficient sensitivity using conventional measures of macro-metabolites such as triglyceride or glucose, but can be sensitively detected utilizing metabonomics. For instance, the effect of strenuous exercise on 420 circulating molecules has been explored in young men. Thirty-four metabolites were identified as possible biomarkers of strenuous exercise, specifically glycerol and asparagine.53 Exploiting metabonomics in the younger population will be of enormous value both to furthering our understanding of the metabolic responses to PA in lean and obese and to expanding our ability to understand the physiology underlying these. 6. Becoming physically active Although the mechanisms underlying reductions in PA are not well understood in the obese children, there are numerous studies documenting the health benefits of becoming physically active. Health benefits are wide-ranging from improvements in lipid and glucose metabolic profiles and insulin resistance,54 to improved endothelial function55 and augmented respiratory function.56 Health outcomes such as these have usually occurred independent of changes in BMI. PA intervention has been shown to result in reductions in adiposity;57,58 however, caution is warranted in interpreting outcomes given many are related to reductions in BMI. It may be time for the focus to be shifted away from BMI as a marker of intervention success, and attention paid to the interplay between health related outcomes and alterations in quantitative aspects of muscle, muscle metabolism and muscle signaling. Whilst there are numerous potential health benefits arising from being physically active, getting obese youngsters to
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become active remains a challenge. The lack of success of many interventions illustrates just how difficult it is to create an intervention strategy that is of sustained interest to the pediatric population.59 Much of the previous intervention work with obese youngsters has relied on an adult evidencebase and although short-term success is regularly apparent, longer-term adherence has been limited.60,61 Consideration of the differences in the obese children’s physiology and their PA patterns have been largely ignored, but in order to successfully deliver PA programmes to obese young people these require attention. 7. Summary Our current understanding of the influence obesity has upon PA in children is primitive and lacks mechanistic explanation. In this review we have proposed that being obese results in changes to skeletal muscle that create a cascade of cellular metabolic alterations, impacting upon the obese children’s ability to be physically active. Whether these changes occur solely because of shifts in body composition in the obese, or whether the disruptions noted in skeletal muscle metabolism occur because of the combined influence of shifts in body composition and inadequate PA is, to date, unknown. Establishing the causal relationship between obesity and physical inactivity is imperative for curbing the obesity epidemic and will require extending our knowledge of how body composition changes with obesity in the child, and how these changes impact upon PA. Importantly, it will require examination of the mechanistic basis of PA in the obese. The dearth of information on the role skeletal muscle metabolism may play in obesity and the emergence of new technologies allowing cellular and metabolite mechanisms to be explored provides plenty of scope for future work. References 1. World Health Organisation. World health statistics 2012. Available at: http:// www.who.int/gho/publications/world_health_statistics/2012/en/ [accessed 16.05.12]. 2. Cheng YJ, Tsung OC. Epidemic increase in overweight and obesity in Chinese children from 1985 to 2005. Int J Cardiol 2009;132:1e10. 3. Tremblay MS, Colley RC, Saunders TJ, Healy GN, Owen N. Physiological and health implications of a sedentary lifestyle. Appl Physiol Nutr Metab 2010;35:725e40. 4. Sedentary Behaviour Research Network. Letter to the editor: standardized use of the terms “sedentary” and “sedentary behaviours”. Appl Physiol Nutr Metab 2012;37:540e2. 5. Dencker M, Thorsson O, Karlsson MK, Linde´n C, Eiberg S, Wollmer P, et al. Daily physical activity related to body fat in children aged 8e11 years. J Pediatr 2006;149:38e42. 6. Ness AR, Leary SD, Mattocks C, Blair SN, Reilly JJ, Wells J, et al. Objectively measured physical activity and fat mass in a large cohort of children. PLoS Med 2007;4:e97. 7. Jimenez-Pavon D, Kelly J, Reilly JJ. Associations between objectively measured habitual physical activity and adiposity in children and adolescents: systematic review. Int J Pediatr Obes 2010;5:3e18. 8. Wilks DC, Besson H, Lindroos AK, Ekelund U. Objectively measured Physical activity and obesity prevention in children, adolescents and adults: a systematic review of prospective studies. Obes Rev 2010;12:e119e29.
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A.M. McManus and R.R. Mellecker 59. van Sluijs E, McMinn A, Griffin S. Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials. BMJ 2008;42:653e7. 60. Summerbell C, Waters E, Edmunds L, Kelly S, Brown T, Campbell KJ. Interventions for preventing obesity in children. Cochrane Database Syst Rev 2005. http://dx.doi.org/10.1002/ 14651858.CD001871.pub2. 61. Waters E, de Silva-Sanigorski A, Hall BJ, Brown T, Campbell KJ, Gao Y, et al. Interventions for preventing obesity in children. Cochrane Database Syst Rev 2011. http://dx.doi.org/10.1002/14651858.CD001871.pub3.