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Etiopathogenesis of childhood obesity


Authors: I. Aldhoon Hainerová 1;  H. Zamrazilová 2
Authors‘ workplace: Klinika dětí a dorostu 3. LF UK a FN Královské Vinohrady, Praha 1;  Endokrinologický ústav, Praha 2
Published in: Čes-slov Pediat 2019; 74 (2): 70-76.
Category:

Overview

Obesity is a multifactorial disorder which is characterized by an increased accumulation of body fat. The interaction of genetic, metabolic, socio-economic and environmental factors plays a major role in the development of obesity. The body weight is substantially influenced by genetic factors. It is estimated that 60–80% of the body mass index is the result of genetic background. There exist solely genetically determined forms of obesity, either Mendelian inherited syndromes or monogenic forms of obesity. Both cases present with early-onset severe obesity. In most of the syndromes there are congenital developmental defects of organs and various degree of mental retardation. On the contrary, monogenic forms of obesity in most cases do not present with a broad phenotypic characterization.

Endocrine disorders associated with weight gain constitute only a small proportion of all cases of childhood obesity. They should be considered if an individual presents with a slow growth rate. A rapid increase in body weight, the presence of hyperphagia and other signs of central nervous system involvement are found in hypothalamic obesity. Several long-term used medications lead to an increased fat mass accumulation either by stimulation of center of hunger or by promoting adipogenesis. Additionally, prenatal factors, including mother’s pre-gestational body weight and nutrition, intrauterine programming and epigenetic factors may impact offspring’s body weight later in life. Inadequate eating practices, inefficient degree of regular physical activity and sedentarism are associated with increased body weight. More than eighty risk factors of obesity have so far been identified.

This review aims at presentation both, the widely known etiopathogenetic factors as well as those less revealed. There is not only an interaction among risk factors themselves but also with the individual genetic predisposition. Researchers and clinicians should therefore search for risk factors possibly associated with body weight gain in each obese patient.

Keywords:

Genetics – Childhood obesity – etiopathogenesis – obesity risk factors – adenovirus


Sources
  1. Hainer V, Bendlová B, Hainerová I, et al. Úloha genetických faktorů v patogenezi a léčbě obezity. DMEV 2006; Suppl 1: 56–64.
  2. Segal NL, Feng R, McGuire SA, et al. Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings. Int J Obes (Lond) 2009; 33: 37–41.
  3. Skytthe A, Kyvik K, Holm NV, et al. The Danish Twin Registry: 127 birth cohorts of twins. Twin Res 2002; 5: 352–357.
  4. Stunkard AJ, Sorensen TI, Hanis C, et al. An adoption study of human obesity. N Engl J Med 1986; 314: 193–198.
  5. Yanovski JA. Pediatric obesity. An introduction. Appetite 2015; 93: 3–12.
  6. Kaur Y, de Souza RJ, Gibson WT, et al. A systematic review of genetic syndromes with obesity. Obes Rev 2017; 18 (6): 603–634.
  7. Hainerová I. Vznik obezity na základě mutací genů ovlivňující energetickou bilanci. Čas Lék Čes 2007; 146: 240–245.
  8. Hainerová I, Lebl J. Monogenní formy obezity. DMEV 2004; 4: 188–193.
  9. Doche ME, Bochukova EG, Su HW, et al. Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest 2012; 122: 4732–4736.
  10. Feuillan PP, Ng D, Han JC, et al. Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance. J Clin Endocrinol Metab 2011; 96: E528–E535.
  11. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348: 1085–1095.
  12. Hainerová I, Larsen LH, Holst B, et al. Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysis. J Clin Endocrinol Metab 2007; 92 (9): 3689–3696.
  13. Asai M, Ramachandrappa S, Joachim M, et al. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science 2013; 341: 275–278.
  14. Savastano DM, Tanofsky-Kraff M, Han JC, et al. Energy intake and energy expenditure among children with polymorphisms of the melanocortin-3 receptor. Am J Clin Nutr 2009; 90: 912–920.
  15. Han JC, Thurm A, Golden Williams C, et al. Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome. Cortex 2013; 49: 2700–2710.
  16. Yeo GS, Connie Hung CC, Rochford J, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 2004; 7: 1187–1189.
  17. Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map. The 2005 update. Obesity 2006; 14: 529–644.
  18. Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937–948.
  19. Bouchard C, Tremblay A, Despres JP, et al. The response to long-term overfeeding in identical twins. N Engl J Med 1990; 322: 1477–1482.
  20. Hainer V, Stunkard AJ, Kunesova M, et al. Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins. Int J Obes Relat Metab Disord 2000; 24: 1051–1057.
  21. Hunt SC, Stone S, Xin Y, et al. Association of the FTO gene with BMI. Obesity 2008; 16: 902–904.
  22. Dušátková L, Zamrazilová H, Sedláčková B, et al. Association of obesity susceptibility gene variants with metabolic syndrome and related traits in 1,443 Czech adolescents. Folia Biol (Praha) 2013; 59 (3): 123–133.
  23. Dušátková L, Zamrazilová H, Aldhoon-Hainerová I, et al. A common variant near BDNF is associated with dietary calcium intake in adolescents. Nutr Res 2015; 35 (9): 766–773.
  24. Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinol 2008; 149: 2062–2071.
  25. Tanofsky-Kraff M, Han JC, Anandalingam K, et al. The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr 2009; 90: 1483–1488.
  26. Smemo S, Tena JJ, Kim KH, et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 2014; 507: 371–375.
  27. Ludwig DS, Currie J. The association between pregnancy weight gain and birthweight. A within-family comparison. Lancet 2010; 376: 984–990.
  28. Finch CE, Loehlin JC. Environmental influences that may precede fertilization: a first examination of the prezygotic hypothesis from maternal age influences on twins. Behav Genet 1998; 28: 101–106.
  29. Symonds ME, Pearce S, Bispham J, et al. Timing of nutrient restriction and programming of fetal adipose tissue development. Proc Nutr Soc 2004; 63: 397–403.
  30. Patterson ML, Stern S, Crawford PB, et al. Sociodemographic factors and obesity in preadolescent black and white girls: NHLBI’s Growth and Health Study. J Natl Med Assoc 1997; 89: 594–600.
  31. Yu Z, Han S, Zhu J, et al. Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity. A systematic review and meta-analysis. PLoS One 2013; 8: e61627.
  32. Barker DJ. The origins of the developmental origins theory. J Int Med 2007; 261: 412–417.
  33. Greening JE, Storr HL, McKenzie SA, et al. Linear growth and body mass index in pediatric patients with Cushing’s disease or simple obesity. J Endocrinol Invest 2006; 29: 885–887.
  34. Bonfig W, Kann P, Rothmund M, et al. Recurrent hypoglycemic seizures and obesity: delayed diagnosis of an insulinoma in a 15 year-old boy – final diagnostic localization with endosonography. J Pediatr Endocrinol Metab 2007; 20: 1035–1038.
  35. Hung CC, Luan J, Sims M, et al. Studies of the SIM1 gene in relation to human obesity and obesity-related traits. Int J Obes Obesity 2007; 31 (3): 429–434.
  36. Srinivasan S, Ogle GD, Garnett SP, et al. Features of the metabolic syndrome after childhood craniopharyngioma. J Clin Endocrinol Metab 2004; 89: 81–86.
  37. Maayan L, Correll CU. Weight gain and metabolic risks associated with antipsychotic medications in children and adolescents. J Child Adolesc Psychopharmacol 2011; 21: 517–535.
  38. Keith SW, Redden DT, Katzmarzyk PT, et al. Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond) 2006; 30 (11): 1585–1194.
  39. Gubbels JS, van Assema P, Kremers SP. Physical activity, sedentary behavior, and dietary patterns among children. Curr Nutr Rep 2013; 2: 105–112.
  40. Ottevaere C, Huybrechts I, Benser J, et al. Clustering patterns of physical activity, sedentary and dietary behavior among European adolescents: The HELENA study. BMC Publ Health 2011; 11: 328–338.
  41. Reilly JJ, Armstrong J, Dorosty AR, et al. Early life risk factors for obesity in childhood: cohort study. BMJ 2005; 330 (7504): 1357.
  42. Dhurandhar NV, Kulkarni P, Ajinkya SM, et al. Effect of adenovirus infection on adiposity in chicken. Vet Microbiol 1992; 31: 101–107.
  43. Hainer V, Hainerová IA, Zamrazilová H. Role of infection in the pathogenesis of obesity. Cas Lek Cesk 2012; 151 (12): 563–567.
  44. Hainer V, Zamrazilová H, Kunešová M, et al. Obesity and infection: reciprocal causality. Physiol Res 2015; 64 (Suppl 2): S105–S119.
  45. Aldhoon-Hainerová I, Zamrazilová H, Atkinson RL, et al. Clinical and laboratory characteristics of 1179 Czech adolescents evaluated for antibodies to human adenovirus 36. Int J Obes (Lond) 2014; 38 (2): 285–291.
  46. von Kries R, Toschke AM, Wurmser H, et al. Reduced risk for overweight and obesity in 5- and 6-years-old children by duration of sleep – a cross-sectional study. Int J Obes Relat Metab Disord 2002; 26: 710–716.
  47. Gangwisch JE, Malaspina D, Boden-Albala B, et al. Inadequate sleep as a risk factor for obesity: analysis of the NHANES I. Sleep 2005; 28: 1289–1296.
  48. Spiegel K, Tasali E, Penev P, et al. Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med 2004; 141: 846–850.
  49. Pelletier C, Imbeault P, Tremblay A. Energy balance and pollution by organochlorines and polychlorinated biphenyls. Obes Rev 2003; 4: 17–24.
  50. Noren K, Meironyte D. Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20–30 years. Chemosphere 2000; 40: 1111–1123.
  51. Jessen AB, Buemann B, Toubro S, et al. The appetite-suppressant effect of nicotine is enhanced by caffeine. Diab Obes Metab 2005; 7: 327–333.
  52. Centers for Disease Control and Prevention. Cigarette smoking among adults – United States, 2002. Morb Mortal Wkly Rep 2004; 53: 427–431.
  53. Hawkins SS, Cole TJ, Law C. An ecological systems approach to examining risk factors for early childhood overweight. Findings from the UK Millennium Cohort Study. J Epidemiol Comm Health 2009; 63: 147–155.
  54. Ravussin E, Valencia ME, Esparza J, et al. Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care 1994; 17: 1067–1074.
  55. Popkin BM, Udry JR. Adolescent obesity increases significantly in second and third generation U.S. immigrants. The National Longitudinal Study of Adolescent Health. J Nutr 1998; 128: 701–706.
  56. Pine DS, Goldstein RB, Wolk S, et al. The association between childhood depression and adulthood body mass index. Pediatrics 2001; 107: 1049–1056.
  57. Di Lorenzo L, De Pergola G, Zocchetti C, et al. Effect of shift work on body mass index: results of a study performed in 319 glucose-tolerant men working in a Southern Italian industry. Int J Obes Relat Metab Disord 2003; 27: 1353–1358.
  58. Arenz S, Ruckerl R, Koletzko B, et al. Breast-feeding and childhood obesity – a systematic review. Int J Obes Relat Metab Disord 2004; 28: 1247–1256.
  59. Zemel MB, Thompson W, Milstead A, et al. Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults. Obes Res 2004; 12: 582–590.
  60. Friedman JM. A war on obesity, not the obese. Science 2003; 299 (5608): 856–858.
Labels
Neonatology Paediatrics General practitioner for children and adolescents
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