Eur J Pediatr (2000) 159: [Suppl 1] S35S44

ILSI 2000

REVIEW

Claudio Maeis

Aetiology of overweight and obesity in children and adolescents

Abstract The epidemic diusion of obesity in industrialised countries has promoted research on the aetiopathogenesis of this disorder. The purpose of this review is to focus mainly on the contribution that European research has made to this eld. Available evidence suggests that obesity results from multiple interactions between genes and environment. Parents obesity is the most important risk factor for childhood obesity. Twin, adoption, and family studies indicated that inheritance is able to account for 25% to 40% of inter-individual dierence in adiposity. Single gene defects leading to obesity have been discovered in animals and, in some cases, conrmed in humans as congenital leptin deciency or congenital leptin receptor deciency. However, in most cases, genes involved in weight gain do not directly cause obesity but they increase the susceptibility to fat gain in subjects exposed to a specic environment. Both genetic and environmental factors promote a positive energy balance which cause obesity. The relative ineciency of self-adapting energy intake to energy requirements is responsible for fat gain in predisposed individuals. The role of the environment in the development of obesity is suggested by the rapid increase of the prevalence of obesity accompanying the rapid changes in the lifestyle of the population in the second half of this century. Early experiences with food, feeding practices and family food choices aect children's nutritional habits. In particular, the parents are responsible for food availability and accessibility in the home and they aect food preferences of their children. Diet composition, in particular fat intake, inuences the development of obesity. The high energy density and palatability of fatty foods as well as their less satiating properties promotes food consumption. TV viewing, an inactivity and food intake promoter, was identied as a relevant risk factor for obesity in children. Sedentarity, i.e. a low physical activity level, is accompanied by a low fat oxidation rate in muscle and a low fat oxidation rate is a risk factor of fat gain or fat re-gain after weight loss. Conclusion Further research is needed to identify new risk factors of childhood obesity, both in the genetic and environmental areas, which may help to develop more eective strategies for the prevention and treatment of obesity. Key words Obesity Genetics Child Nutrient balance Energy balance Environment Abbreviations BMI body mass index BMR basal metabolic rate CART cocaine and amphetamine regulated transcript NPY neuropeptide Y PC1 pro-hormone convertase 1 PPARc2 peroxisome-proliferator-activated receptor c2 TEE total energy expenditure
C. Maeis (&) Department of Paediatrics, University of Verona, Polyclinic B Roma, 37134 Verona, Italy e-mail: maeis@borgoroma.univr.it Tel.: ++39-045-8074371; Fax: ++39-045-8200993

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Introduction

``Obesity runs in families, therefore obesity is genetics''. ``Obesity is the consequence of gluttony and sloth''. ``The extraordinary eciency in storing energy in spite of a reasonable food intake showed by obese children suggests a metabolic defect as the cause of their obesity''. These are some common beliefs of the public on the origin of obesity. Progress in obesity research has revealed that most of the circulating myths about the aetiology of childhood obesity are not true [5]. Obesity is a multifactorial disease and its development is due to multiple interactions between genes and environment. In fact, the development of fat gain is a complex phenomenon which is regulated and aected by several mechanisms and factors. The purpose of the present paper is to review some aspects of the aetiopathogenesis of childhood obesity. These have been recently reviewed by others [98], but this review mainly focuses on the contribution that European research has made to this eld.
Genetic risk

Children of obese parents have a higher risk of becoming obese than do children of non-obese parents [33, 38, 57, 70, 87, 102]. In particular, identical twins of obese parents are more likely to become obese than those of non obese parents, suggesting a genetic factor to obesity [13]. Studies in adoptees showed that adopted children as adults had greater similarity in body mass index (BMI) and other features with their biological parents than with their adopting parents [105]. Approximately 70% of the variance of the inheritance of BMI among monozygotic twins reared apart, which is not accounted for by covariates (age, sex, their interactive eect, source of data), may be attributed to genetic variation [3]. In a recent review on twin, adoption and family studies, BMI inheritance has been proposed to account for 25% to 40% of the inter-individual variability [14]. Genes involved in weight gain generally increase the susceptibility to fat gain in subjects exposed to a specic (high risk) environment more than they directly cause obesity. Linkage studies have identied several chromosomes associated with the obese phenotype [17]. Research eorts are now focused on the identication of single genes involved in the development of obesity and their function although, given the multifactorial nature of the disease, a single versus multiple gene defect is unlikely, at least in the majority of cases [17]. Some examples of single gene defects causing obesity have just been discovered in animals as well as humans [14, 15, 80, 108, 113]. These defects may explain some cases of nonsyndromic superobesity in children. In particular, severe leptin (the product of ob gene) deciency has been demonstrated in two grossly obese children, who showed the same mutation in the ob gene [77]. Six months treatment with recombinant-methionyl human leptin

induced signicant weight loss in a 9-year-old girl with severe obesity due to congenital leptin deciency [27]. Congenital leptin receptor deciency has been recently demonstrated in humans [16]. A novel anorectic peptide, cocaine and amphetamine regulated transcript (CART), regulated by leptin has been recently discovered [52]. CART peptide signals satiety in the hypothalamus and interacts with neuropeptide Y (NPY) and other hypothalamic regulators of ingestive behaviour. Recombinant CART peptide, injected intracerebroventricularly in rats, inhibits both normal and starvation induced feeding and completely blocks the feeding response induced by injection of NPY. Further studies in animals and humans may identify a potential application of this discovery to the treatment of obesity. Finally, mutations of pro-hormone convertase 1 (PC1) gene, responsible for the activation of pro-insulin processing, have been recently reported in humans [41]. PC1 is a member of the furin family of endoproteases that activate proproteins by cleavage of carboxy-terminal moieties. Mutations in the PC1 gene have promoted an autosomal recessive syndrome in a woman, characterised by early-onset obesity, post-absorptive hypoglycaemia, amenorrhoea and sleepiness, with complete absence of insulin and extremely elevated pro-insulin circulating levels [41]. In mice, the fa/fa phenotype, which is associated with a mutation in its carboxypeptidase E gene, is very similar to this syndrome [80]. After cleavage by PC1 (or related enzymes), carboxypeptidase E removes basic residues exposed at the carboxy-terminus of proteins. The mechanisms by which this defect causes obesity are still unknown. Relevance of pre-adipocyte dierentiation mechanisms in the development of obesity has been highlighted from the results of recent studies. In particular, a mutation (Pro115Gln) of the peroxisome-proliferator-activated receptor c2 (PPARc2) gene has been recently demonstrated [94]. PPARc2 is a nuclear hormone receptor which is a powerful regulatory factor of the differentiation from pre-adipocyte to adipocyte [103]. This mutation promotes a reduction of the inactivation of PPARc2 with an enhanced activity of the protein and an acceleration of the dierentiation of pre-adipocytes, promoting obesity [94]. Another mutation in the same gene (Pro12Ala) was associated with a reduced receptor activity and a lower BMI in adults [22]. Other transcription proteins expressed in adipogenesis were found to enhance the expression of PPARc2, like CCAATenhancer-binding protein alpha, which in addition promotes the synthesis of an intracellular fatty acid-binding protein, and the dierentiation-dependent factor 1, which induces fatty acid synthetase and lipoprotein lipase [40, 46].
Environmental risk

Childhood obesity tends to persist into adulthood in 30% to 60% of cases [101]. In particular, the risk is higher in children of obese parents [33, 38, 57, 70, 87,

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102] and it is proportionally higher in older and fatter children [89, 112]. Although genetics may explain part of this evidence, several environmental factors signicantly aect this phenomenon. The rst physiological contact of the child with the environment is in the uterus. In fact, during pregnancy the fetus widely interacts with the mother and her metabolism and may be aected by it, even with respect to the development of the metabolic regulatory mechanisms [7, 85]. During gestation, hypothalamic centres of hunger and satiety are dierentiated and hyperplasia of adipose tissue occurs (third trimester). Over- or under-feeding in pregnancy has been associated with the development of obesity in later life [86, 92]. The rush of the Second World War events between October 1944 and May 1945 in the west Netherlands induced a serious famine. The longterm eects of famine on young adult males born from women who were pregnant during that period have been studied [92]. Undernutrition during the rst and the second trimester of pregnancy was associated with a higher prevalence of obesity in adults at the age of 19 whereas undernutrition occurring during the last trimester of pregnancy was not associated with subsequent obesity [92]. In contrast, children born to mothers who had diabetes during pregnancy were more frequently obese, independent of other factors, than children of mothers who were not diabetic during pregnancy [86]. Therefore hyperglycaemia and hyperinsulinaemia exposure during fetal life may be a risk factor for obesity in later life. After birth, the method of feeding and weaning may theoretically inuence the risk of obesity. Breast feeding, which for a number of reasons is the best food for infants during the rst months of life, is not proved to have a protective eect on the development of obesity later in life [51]. Although early experiences with food, the association of food avours with the context and the consequences of eating may potentially aect food acceptance and food habits of the child, precocious introduction of solid foods also did not correlate with obesity in older children and adolescents [2, 7, 10, 51, 70, 85, 86, 89, 101, 106, 112]. Further prospective studies, performed in dierent European populations with dierent infant nutrition modalities are needed to formulate a denitive statement on this matter. It has been frequently reported that feeding practices highly inuence children's food choices. Family lifestyle and food habits play a role in developing children's food preferences and this may aect their body weight. In fact, parents' adiposity and fat intake are in many ways associated with their children's adiposity and fat intake, which suggests that familial similarities in food composition may partially explain familial patterns of adiposity [81]. Parents are responsible for food availability and accessibility in the home. Moreover, children's eating habits are modied by the attitudes and behaviour of parents, peers, siblings, and relatives who live with them [9, 48]. Parents' encouragement to eat promotes fat gain in their children [48]. TV viewing, with advertisements for food products and providing a vari-

ety of models and messages about eating, have some eect a food preferences and food selection by children [19, 107] although the picture is complex and should be seen in the context of the family [19]. Recently, signicant interactions between advertisement type and overweight were observed on ratings of perceived health and appetite for sweets [55]. Fat mass uctuates physiologically between seasons and geographical and climatic inuences on the prevalence of obesity in children have been suggested [24]. However, comparative data collected in the dierent European areas to evaluate these risk factors are scarce [60]. Available data suggest that the prevalence of childhood obesity is higher in the east and in the south of Europe than in the west and in the north of the continent [60]. The reasons for this dierence which needs to be conrmed have to be identied. The relationship between the socioeconomic level of the family and childhood obesity showed somewhat inconclusive results [53, 57, 58, 62, 70, 88, 95]. When parents' BMI is controlled in the statistical analysis, the relationship between the socioeconomic level of the family and childhood obesity usually disappears because low family income and parents' overweight are frequently associated [57, 70, 95]. However, rearing area was found to have a much stronger inuence on the risk of overweight in young adulthood than parental education and occupation [57]. In fact, the risk of overweight was highly increased for individuals reared in an area with poor quality of dwellings compared to those from a good area, even when controlling for the eect of parents' education and occupation [57]. Moreover, parental neglect during childhood predicts obesity in young adulthood, independent of age and BMI in childhood, gender, and social background [58]. Several reports suggest that sedentary behaviour is common in a relevant portion of children today and it has been identied as a signicant predictor of weight gain later in life, although large longitudinal studies, in which accurate techniques to measure physical activity have been used, are not available [60, 74, 79, 90]. Indeed, sedentary behaviour may precede as well as accompany obesity. Several reasons, mainly social, environmental and psychological, may contribute to explain the sedentary lifestyle widespread among children. In particular, low physical activity levels have been associated directly with TV viewing and inversely with time spent outdoors [36, 99]. Children with physically active parents are usually far more active than children whose parents are inactive [78]. The physical activity level of children is also aected by the socioeconomic conditions of the family as well as availability of facilities and equipment access, and peer inuences [50].
Energy and nutrient balance

The physiological growth of a child is genetically programmed in such a way that major variations in body

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composition normally occur between birth and adulthood. In particular, fat mass, expressed as a percentage of body weight, increases dramatically from 14% at birth to 25% at the age of 6 months; then it decreases progressively, reaching its nadir usually at the age of 6 years [30]. Subsequently, the relative fat mass increases again until maturity. A sophisticated regulatory system controls this process, whose function is to allow the subject to reach the best body composition necessary to perform the work and reproductive activities typical of adult life. Evidence in humans shows that automatic, involuntary mechanisms are activated when feeding occurs below or beyond one's requirements and which help to maintain the weight genetically programmed for an individual exposed to that specic environment [93]. The existence of a compensatory mechanism that opposes the maintenance of an altered body weight in children has not yet been investigated. However, children seem to have an ecient self-regulation mechanism of food intake which tends to stabilise their energy intake. In fact, 6 days free access to food they like, in a group of children, did not promote sensible variations of their total daily energy intake in spite of a large dierence between energy intake of single meals [11]. Epidemiological data have unequivocally demonstrated that a progressively larger cohort of children living in industrialised countries is no longer following physiological growth patterns, showing a greater adiposity than that of the reference child [60]. In children who become obese, the mechanism for self-regulation of fat mass, if present, has not been ecient or it has been skilfully dodged. Several genetic, environmental and metabolic factors may be involved in the development of this phenomenon. However, for physical reasons, i.e. the rst law of thermodynamics, each of the risk factors involved in fat gain must necessarily promote, as an epiphenomenon, a positive energy balance. Even a prolonged minimal positive energy balance is able to induce fat storage; e.g. storing less than 2% of her energy intake every day, a 6-year-old girl is able to increase her fat mass by 30% in 1 year. Therefore, subtle modications of the mechanism of energy balance, which at present are dicult to identify, seems to be the main responsible for fat gain and obesity development. Energy balance is dened as the dierence between energy intake and total daily energy expenditure (TEE). The value (positive or negative respectively) of this balance normally uctuates with time during the day. The forms by which energy is consumed and used by the body are those of macronutrients: protein, fat and carbohydrate. In fact the contribution of bre, which is another source of energy (1.5 kcal/g), is quantitatively negligible for current average bre intake. Another high energy nutrient like alcohol (7 kcal/g) has not been included because alcohol intake is unusual, at least in young children. Taking the body as an isolated system, independent of intermediary metabolic processes of breakdown and resynthesis of nutrients and molecules, the balance between nutrients entering the system and

nutrients oxidised into the system gives energy balance. On these bases, energy balance may be given as the sum of the balance of the three nutrients1 [29]. It is interesting to note that carbohydrate and protein intake induce, respectively, carbohydrate and protein oxidation. Moreover, carbohydrate is not able to promote de novo lipogenesis except in prolonged carbohydrate overfeeding conditions when the carbohydrate stores are fully saturated [1]. On the contrary, fat intake is not able to induce fat oxidation [100]. Therefore, carbohydrate and protein balance are eciently selfregulated whereas fat balance is aected by the balance of the other two nutrients and depends strictly on them. This characteristic of nutrient metabolism has an important impact on the pathophysiology of obesity. In fact, the oxidative hierarchy shown by the body which shows its preference for the oxidation of carbohydrate and protein rather than that of fat, independently of fat intake, suggests a relevant responsibility of fat balance in promoting fat gain [28]. Fat storage occurs contemporary with fat intake, minus the fat oxidation rate, which is dened as the dierence between TEE and the carbohydrate and protein oxidation rate. In other words, ingested fat is preferentially stored with the exception of that which is oxidised, which is independent of fat intake but dependent on the amount of carbohydrate and protein ingested and oxidised (Fig. 1).
Energy and fat intake

Food consumption pro capite in developed countries is not comparable to that of developing countries [47]. In the former, overfeeding is the norm. However, estimates of daily energy intake in children living in the industrialised countries were not usually able to show relative hyperphagia of obese subjects [66, 84]. This might be at least partially explained by the relative inaccuracy of the methods actually available to estimate food intake. In fact, studies of energy balance conducted in free living conditions have revealed that obese children, as well as obese adolescents, usually have a higher daily TEE than non-obese subjects, a clear demonstration of the underestimation of their self-reported food intake [6, 61, 72]. This nding makes it imperative to validate food intake declared by people before drawing any conclusions from the studies. This is particularly true in the case of pre-obese subjects or in the developing phase of fat gain, where a relatively small positive energy balance, dicult to detect, justies fat gain. Moreover, since children of obese parents run the highest risk of becoming obese [33, 37, 38, 70, 87, 102], and since obese adults too show a tendency to underestimate food intake
Energy balance D protein balance + D carbohydrate balance + D fat balance D energy stored, where D nutrient balance D nutrient intake ) D nutrient oxidation and D energy stored D protein stored + D carbohydrate stored + D fat stored. D delta, expresses the time dependency of the variable.
1

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insulin-like growth factor-1 and insulin secretion, which promote fat storage and the proliferation of mature adipocytes [96, 111]. Further studies are necessary to verify this hypothesis. Finally, the relationship between habitual frequency of eating and obesity has been explored to test the hypothesis that there must be an inverse association between meal frequency and overweight [8]. Several recently reviewed studies failed to show dierence of TEE between nibbling and gorging individuals [8]. Moreover, it was suggested that any effects of meal pattern on the regulation of body weight was probably mediated through eects on the food intake side of the energy balance equation [8]. Finally, evidence exists that children who regularly practice physical activity had more structured food patterns than those who do not [23].
Fig. 1 Metabolic fate of fat intake and relationship to carbohydrate and protein oxidation and skeletal muscle activity

Energy and fat oxidation

[56], data obtained from obese parents regarding the food intake of their ospring need to be carefully validated with the contemporary measurement of their requirements. In spite of the above-mentioned problems concerning the inaccuracy of the methods for estimating food intake in free-living children and postulating that a selective under-reporting of a specic nutrient is possible but unlikely, the association between nutrient intake and fat gain may be explored separating energy intake into the three macronutrients: carbohydrates, lipids and proteins. Several studies on food intake in European children showed that, in general, an overconsumption of fat and protein, especially of animal origin, and an underconsumption of bre with respect to national recommended daily allowances is common [4, 43, 45, 60, 84]. Evidence exists that obese children show a certain preference for a fatty diet [34, 84]. A fatty diet has frequently been associated with fat gain and obesity [34, 49, 59]. Relative fat intake was directly proportional to the level of adiposity [66]. A physiological situation in which a high-fat diet is associated with fat gain is early infancy, when the infant takes only milk (fat >50% of human milk energy) and his fat mass quadruplicates in just 4 months [30]. Fatty foods have a higher energy density and are often palatable [97]. These characteristics promote food consumption. Moreover, fat is less satiating than proteins or carbohydrates, and self-compensation by adjusting subsequent intake is less likely after a high-fat meal [12]. Finally, the relatively high fat intake causes a certain energy saving due to the lower thermogenesis induced by fat intake (3% of energy content of fat ingested) compared to that induced by carbohydrate or protein (5%8% and 20%25%, respectively) [42]. In toddlers and young children, the protein intake has been found to be much higher than recommended [60, 96] which led to a hypothesis for a role for a high protein to fat intake ratio in the development of obesity [96]. An interesting nding is that protein intake stimulates

The prevalence of childhood obesity is growing, even though surveys on food intake have failed to show progressively higher energy intake in children [21, 60]. Two main factors may contribute to explain this apparent discrepancy. One factor is the inaccuracy of the estimation of food intake of overweight children which potentially aects the average energy intake of children leading to an overall underestimation of energy intake [6, 61]. Another factor is the contemporary reduction in total energy requirements and fat oxidation rate in industrialised populations. Energy requirements are equal to energy expenditure (plus energy to growth) [26, 109]. Therefore, body weight and fat gain are necessarily due to an energy intake greater than TEE. Each of the components of TEE: basal metabolic rate (BMR), thermogenesis, and the energy expenditure for physical activity, may be relatively reduced in pre-obese children2. However, several studies performed in prepubertal children and adolescents failed to nd a higher metabolic eciency in obese or post-obese subjects. Studies on BMR, i.e. the main component of TEE, did not show a dierence among obese, post-obese and nonobese children when body composition, in particular the metabolic active tissue (fat-free mass), was included as a covariate in the statistical analysis [63]. Moreover, children of an obesity-prone population like Pima Indians had BMR comparable to that of Caucasian children having the same age, sex and body composition suggesting that a reduced BMR may not be involved in the excess fat gain of these children [31]. Thermogenesis induced by a standardised meal was inconstantly and slightly reduced in obese than in non-obese children [69, 76] whereas meal-induced thermogenesis was no dierent in post-obese and non-obese children [64]. This
2

Energy expenditure for growth is negligible in respect to TEE, except in the 1st year of life and during puberty. Moreover, a reduced energy expenditure for growth is unlikely in pre-obese children.

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nding suggests, by implication, that a reduced mealinduced thermogenesis is unlikely in pre-obese children. This does not exclude the possibility that diet composition may aect meal-induced thermogenesis and theoretically favour energy storage [42]. Therefore, most of the relatively reduced energy requirements of pre-obese children in comparison with their energy intake is reasonably considered to be due to their lower energy expenditure for physical activity which is the only discretionary component of TEE. This nding is not surprising because sedentary behaviour is common in children today. Obese children are usually less physically active than non-obese children [44, 60, 73, 74] (Fig. 2) and time devoted to sedentary activities has been directly associated with adiposity levels [67] (Fig. 3). However, the proportion of TEE devoted to physical activity is comparable in obese and non-obese children in both the United States and in Europe [6, 72]. The apparent discrepancy between more frequent sedentary behaviour of obese children and the proportionally comparable energy expenditure for activity by obese and non-obese children may be explained by the higher energy cost of weight-bearing activities per unit of exercise due to the heavier body that obese subjects have to move [68]. Maximal cardiorespiratory capacity per unit of fat-free mass is not signicantly dierent in obese and non-obese non-trained children [20, 71]. Therefore skeletal muscle cells of obese children have a maximal oxidative capacity similar to that of non-obese children, independent of their adiposity. The metabolic activity of skeletal muscle plays a key role in the regulation of fat balance. In fact, skeletal muscle oxidises a relevant amount of fat every day. A high fat oxidation rate plays a protective role in the risk of weight gain as well as in the risk of weight re-gain after weight loss [32, 114]. On the contrary, a high carbohydrate oxidation rate has been suggested as a risk factor for weight gain or re-gain [32, 114]. Physical

activity, especially regular exercise, promotes fat oxidation in the muscle as well as post-exercise oxygen consumption [35, 104]. Moreover, physical activity was associated with a lower fat/carbohydrate intake ratio in 10-year-old children [23]. Together with physical activity, adiposity per se is able to increase fat oxidation by increasing the availability of free fatty acids in the circulation released by the increased number of fat cells, which promotes substrate competition between free fatty acids and glucose in the muscle, favouring insulin resistance [91]. A signicant association between adiposity and the post-absorptive fat oxidation rate in obese children and adolescents has been found [54, 65, 75]. The post-absorptive fat oxidation rate is directly proportional to fat mass in these children [65]. Data on the overall fat oxidation rate measured over 24 h in freeliving conditions are not yet available on children.
The origin of childhood obesity: a comparison between North American and European experiences

Data on the prevalence of obesity obtained in representative samples of North American and European children using the same methods and the same reference values for denition of obesity are not available. Therefore, it is not possible to assess whether the prevalence of childhood obesity is dierent in the United States and in Europe [60, 110], although indirect evidence suggest that such a dierence may exist. Obesity is the result of the eect of multiple environmental and psychological factors on a predisposing genetic substrate. Therefore, it is possible that genetic as well as environmental factors (geographical, sociocultural, nutritional, lifestyle, etc.) may be dierent in the populations of the two continents. Renewed attention to the genetic factors associated with obesity have been recently given both in the United States and in Europe.

Fig. 2 Time spent in sedentary and non sedentary behaviour in a group of obese and non-obese pre-pubertal children (modied from [73])

Fig. 3 Relationship between adiposity (% fat mass) and nonsleeping time spent in sedentary behaviour (min/day) in a group of prepubertal boys (modied from [67])

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Both are multiracial countries characterised by high immigration uxes and where the various ethnic groups are dierently distributed. Heterogeneity of genetic background may contribute to explain the dierences in the prevalence of obesity among races living in the same country and exposed to a mostly similar environment. Three studies, using the genome scanning technique which allows identication of candidate genes and establishment of their proximity to quantitative trait loci that aect the ``obese'' phenotype [17], were recently conducted in America (in Pima Indians and in MexicanAmericans), and in Europe (in the French), respectively [18, 39, 83]. These three studies identied dierent genomic regions associated with the obese phenotype. In Pima Indians, identied regions were on the chromosome 3 and 11 [83]; in Mexican-American, regions of chromosome 2 and 8 were involved [18]; in the French, three dierent regions of chromosome 2, 5, and 10 were found [39]. These data demonstrate that several genetic loci may potentially be involved in the development of obesity and that the genetic background may contribute to explain dierences between races in the candidate genes associated with the obese phenotype. Comparative analysis concerning environmental factors associated with childhood obesity in the United States and Europe is not easy given the multi-ethnicity of both societies which promotes deep sociocultural, nutritional and lifestyle dierences among people living in the same country and makes a representative sample of the entire community dicult to obtain. Moreover, Europe still has remarkable dierences in all aspects of sociocultural life, nutritional habits and lifestyle among its nations, especially between the north and south, but also between the east and west (see other chapters). Sedentary behaviour of children living in both Europe and the United States is common. A mean time of 25 h per week spent in front of the TV is for children living in the United States whereas 30% (7%51%) of European children watch TV at least 4 h a day [25, 47]. The longer time of TV viewing of American children, if considered as an index of sedentary behaviour and a risk factor for food intake, may theoretically increase the risk of obesity in American children. Comparative studies on children's food intake conducted with the same methods in representative samples of American and European populations are not available. However, a gross analysis of existing data, taking into account all the limitations of this procedure, seems to suggest that the average diet composition of European children, which shows wide variations among countries [60], is characterised by a fat intake (35%) that is comparable to that reported in the United States (36%) [110]. Further experience has to be accumulated to allow a more accurate comparison between Europe and the United States. Given the accelerated historical progression towards a ``global'' society sustained by technological and economical reasons, the risk factors of obesity should theoretically tend to become the same on both continents and in all European countries. Persistence of cultural traditions

among populations can make the dierence, by promoting or defending it from obesity.

Conclusions

Obesity is the result of an imbalance between nutrient intake and nutrient oxidation. A prolonged minimal positive energy balance is able to induce fat storage. Diet, skeletal muscle activity, and adiposity aect nutrient balance and fat mass. Fat intake is associated with adiposity in children. Fat intake promotes fat gain via several factors: higher food energy density, higher palatability and lower satiating properties, all factors which promote food intake and a hypercaloric diet. Lower thermogenesis induced by fat intake in comparison to that induced by protein and carbohydrate intake may be another contributing risk factor of fat gain. Muscle activity is an important determinant for both energy expenditure and fat oxidation rate. A reduced level of physical activity causes a decreased energy expenditure, i.e. energy requirements. Moreover, muscle is the key fat oxidiser. Reduced muscle activity favours reduced fat oxidation, promoting fat imbalance. Obesity tends to be self-limited. In fact, an enlargement of fat mass has several metabolic consequences which may favour the achievement of a new fat (and energy) balance, resisting further fat gain. Evidence of an increased post-absorptive fat oxidation rate, which can be explained as a compensatory reaction, has been reported in obese children and adolescents. Further research, performed in dierent European countries and focused both on the genetic and environmental factors aecting energy (and fat) balance in children and adolescents, is essential to advancing knowledge in this eld. In particular: 1. Further exploration of human genomes may lead to identify new candidate genes of obesity, favouring the selection of individuals at higher risk of obesity in the population and eventually to identify dierent subgroups of obese children, whose obesity has dierent aetiology; 2. The role of macronutrient intake in the development of childhood obesity is still unclear. Further prospective balance studies are needed for exploring this relationship in the developing phase of fat gain; 3. The comparison of energy and nutrient intakes of children living in dierent European countries in relationship with the prevalence of obesity and evaluated with the same criteria in each country may identify the level of association between the dierent risk factors and obesity and eventually highlight differences in the aetiology of obesity between countries; 4. Investigations of skeletal muscle metabolic activity, in particular fat oxidation, and its role in energy and nutrient balance regulation and appetite regulation, may help clarify the role of physical activity in the development and maintenance of childhood obesity.

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