**3. The etiology of obesity and the risk factors**

Obesity is a multifactorial disease with a complex etiology being involved genetic, environmental, psycho-socio-cultural, neuroendocrine and metabolic factors, intestinal microbiota. The factors involved in its etiology included the 'obesogenic' environment, and the unhealthy dietary behaviors and patterns of physical activity [14].

There is growing interest in the role of experience in early life in the risk of becoming overweight or obese. In children, prenatal life may be a critical period when the long-term regulation of energy balance is permanently 'programmed'. The perinatal parameters and factors implicated in the etiology of obesity include maternal obesity, excessive weight gain in pregnancy, gestational diabetes, and maternal smoking, duration of breastfeeding, rapid infancy weight gain and other cultural or familial factors associated with childhood eating patterns and activity levels [14, 15].

Maternal obesity is a strong predictor of overweight and obesity in children. Obesity in pregnant women was found to be associated to high newborn weight and also causing obesity and metabolic syndrome risk in later life of the individual. Intrauterine growth restriction is associated with the development of central adiposity and adult-onset cardiovascular risk [4, 14].

Child's exposure to passive smoking, since the product conception stage, predisposes to the development of obesity and obesity related diseases as a result [14, 16, 17].

Breastfeeding could help infants to better recognize satiety signals and hence to better selfregulate energy intake. The prevalence and duration of breastfeeding is higher in countries with relatively lower prevalence of childhood obesity such as Sweden, Finland and Austria, in comparison to countries such as Italy, Greece and the UK, where is less [7, 14, 15].

Ethnicity is associated with differences in eating behaviors, preferences, and cultural influences may contribute to obesity among children and youth in minority populations.

The environmental factors are represented by: over-nutrition (high fat, high sugar diets), sedentary lifestyle, short sleep duration, abuse of drugs (antibiotics, corticosteroids, anti-epileptics drugs), smoking and alcohol. Almost all obesity in children is strongly influenced by environmental factors, caused by a sedentary lifestyle or a caloric intake that is greater than needs. However, this explains only a part of obesity risk, but is important targets for treatment such they can be modifiable.

Sugar-sweetened beverages—the literature evidence suggests that consumption of sugarsweetened beverages is an important factor in the development of obesity in some individuals. In the United States, sugar-sweetened beverages supplied an average of 270 kcal/day, representing 10–15% of total caloric intake. In a separate randomized trial on children aged 5–12 (primarily normal weight), consuming one serving of a sugar-free beverage daily was associated with less weight gain and fat accumulation than consuming one serving of a sugarsweetened beverage. Other studies have found that dietary salt intake is associated with increased intake of sugar-sweetened beverages, perhaps because of increased thirst [18, 19].

Data from Eastern European countries indicate the prevalence rate is smaller (15%), but rising. In Lithuania, the Russian Federation, Slovakia and Poland, the overweight and obesity prevalence ranges from 8.46 to 15.8% in children aged 6–12 years. It is likely that the huge economic burden and the associated poverty following the political transition in the 1990s

Obesity is a multifactorial disease with a complex etiology being involved genetic, environmental, psycho-socio-cultural, neuroendocrine and metabolic factors, intestinal microbiota. The factors involved in its etiology included the 'obesogenic' environment, and the unhealthy

There is growing interest in the role of experience in early life in the risk of becoming overweight or obese. In children, prenatal life may be a critical period when the long-term regulation of energy balance is permanently 'programmed'. The perinatal parameters and factors implicated in the etiology of obesity include maternal obesity, excessive weight gain in pregnancy, gestational diabetes, and maternal smoking, duration of breastfeeding, rapid infancy weight gain and other cultural or familial factors associated with childhood eating patterns

Maternal obesity is a strong predictor of overweight and obesity in children. Obesity in pregnant women was found to be associated to high newborn weight and also causing obesity and metabolic syndrome risk in later life of the individual. Intrauterine growth restriction is associated with the development of central adiposity and adult-onset cardiovascular risk [4, 14].

Child's exposure to passive smoking, since the product conception stage, predisposes to the

Breastfeeding could help infants to better recognize satiety signals and hence to better selfregulate energy intake. The prevalence and duration of breastfeeding is higher in countries with relatively lower prevalence of childhood obesity such as Sweden, Finland and Austria, in

Ethnicity is associated with differences in eating behaviors, preferences, and cultural influ-

The environmental factors are represented by: over-nutrition (high fat, high sugar diets), sedentary lifestyle, short sleep duration, abuse of drugs (antibiotics, corticosteroids, anti-epileptics drugs), smoking and alcohol. Almost all obesity in children is strongly influenced by environmental factors, caused by a sedentary lifestyle or a caloric intake that is greater than needs. However, this explains only a part of obesity risk, but is important targets for treat-

Sugar-sweetened beverages—the literature evidence suggests that consumption of sugarsweetened beverages is an important factor in the development of obesity in some individuals.

development of obesity and obesity related diseases as a result [14, 16, 17].

comparison to countries such as Italy, Greece and the UK, where is less [7, 14, 15].

ences may contribute to obesity among children and youth in minority populations.

may have contributed to the relatively low obesity prevalence in Eastern Europe [7].

**3. The etiology of obesity and the risk factors**

100 Adiposity - Epidemiology and Treatment Modalities

dietary behaviors and patterns of physical activity [14].

and activity levels [14, 15].

ment such they can be modifiable.

Television viewing is an environmental influence on the development of obesity in children. Contact of a child with television begins in the newborn stage and tends to increase continuously. In the first year of life, children react to the screen characters with mimics and voice. Toddlers spend approximately 1 h a day watching television, and from the 4th year of life the exposure to other type of media expands and rises significantly to reach 7 out of 24 h per day. The presence of a television in a child's bedroom and any time spent in watching television are directly related to the prevalence of obesity in children and adolescents. A significant association between advert exposure and childhood obesity has been demonstrated in a cross-cultural study which included data from the USA, Australia and eight European countries [18, 20–22].

Video games—the use of PC or console games has been associated with obesity in children. Half of American children have either a DVD, video or game console in their bedroom and, third, a computer with access to Internet [22, 23].

Sleep—there is a reported association between shortened sleep duration and obesity. A causal association arises from a short-term experimental study in which sleep deprivation for 1 week was associated with increased food intake, weight gain and higher leptin levels as compared to the child's usual sleep. Moreover, sleep may have an association with insulin resistance, independent of its association with obesity. The mechanism between sleep duration and obesity has not been well-known, but may comprise dysfunction in serum leptin and/or ghrelin levels, both are involved in the regulation of appetite [4, 18]. A meta-analysis found that sleep is positively associated with fat mass in toddlers. A positive association between nighttime sleep and BMI *z*-scores were observed in the study reported by Kuzik and Carson [24].

Medications that may cause weight gain in children include cortisol and other glucocorticoids, sulfonylureas, tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, such as phenelzine, oral contraceptives, insulin (in excessive doses), thiazolidinediones, risperidone, clozapine [25].

Other environmental factors that have been proposed as possible contributors to obesity include the influences of gut microbiota, toxins and viruses. Due to the influence of gut microbiota, it has been suggested that there exists a relationship between the resident intestinal bacteria and the potential for weight gain. Effect of microbiota may be partially responsible for increased rate of obesity in children born via cesarean section. Intestinal bacteria seem to influence several factors leading to development of obesity complications such us nonalcoholic steatohepatitis, cardiovascular disease and insulin resistance in humans [26]. It has been suggested that obesity can be triggered or worsened by exposure to a virus. Adenovirus 36 increases body fat in several animal models [18].

Other epidemiologic studies highlight the possibility that obesity could be triggered or exacerbated by exposure to environmental endocrine disrupting chemicals (dichlorodiphenyltrichloroethane—DDT and bisphenol A—BPA). Some studies in adults and children establish an association between urinary BPA levels and obesity or obesity related diseases, as well as diabetes and cardiovascular disease [18].

Endocrine disruptors can disturb every level of the endocrine system. They can interrupt the action of enzymes involved in steroidogenesis. The endocrine disruptors inducing obesity are called obesogens and have been revealed to target transcription regulators that function to control intracellular lipid homeostasis as well as proliferation and differentiation of adipocytes. The main group of regulators that are targeted represent a group of nuclear hormone receptors recognized as peroxisome proliferator-activated receptors (PPARα, δ and γ). PPARγ is considered to be the master regulator of adipogenesis and plays key roles in nearly all aspects of adipocyte biology. Other endocrine disruptors are known to promote adipogenesis, but probably do not act through PPARγ, these include BPA, organophosphate pesticides and monosodium glutamate [27].

Hormonal disorders associated with childhood obesity include growth hormone deficiency, growth hormone resistance, hypothyroidism, leptin deficiency or resistance to leptin action, glucocorticoid excess (Cushing syndrome), precocious puberty, polycystic ovary syndrome (PCOS), prolactin-secreting tumors. Furthermore, in obese individuals, dysfunction in the gut-brain hypothalamic axis and ghrelin/leptin hormonal pathway has been proposed to have a role in excess energy intake and abnormal appetite control [28].

#### **3.1. Genetic factors**

Specific syndromes and single gene defects that are linked to obesity in children have been identified. These are very rarely causes of obesity, Generally, monogenic forms of childhood obesity are very rare, accounting for <1% in children. Mutations in only a few genes are known to cause the development of severe obesity in early childhood. Single gene disorders that can cause obesity include deficiency in leptin or its receptor, mutation in leptin gene, deficiency of proopiomelanocortin (POMC), haploinsufficiency receptor 4 and accessory protein receptor 2 of melanocortin, also disorders of protein convertase 1 [4, 18]. The leptin/leptin receptor system regulate food intake through reduce feeding and increased energy expenditure. Some forms of monogenic obesity like congenital leptin deficiency benefits from leptin substitution therapy that leads to significant decrease in weight [29].

Moreover, children with genetic syndromes associated with obesity typically have early onset obesity and characteristic signs on physical examination, including dysmorphic features, developmental delay, short stature or intellectual disability, retinal changes or deafness. The Prader Willi syndrome is the most common among obesity syndromes and is characterized by hypotonia and feeding difficulties during infancy, hyperphagia and obesity developing during early childhood and developmental delay. Other syndromes associated with childhood obesity are Pseudohypoparathyroidism, Laurence Moon Biedl (Bardet Biedl) syndrome, Cohen syndrome, Down syndrome and Turner syndrome [30].
