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Synergy of nature and nurture in the development of childhood obesity

International Journal of Obesity volume 33, pages S53–S56 (2009)Cite this article

Abstract

Epidemiological studies suggest that maternal undernutrition, obesity and diabetes during gestation and lactation can all produce obesity in human offspring. Animal models provide a means of assessing the independent consequences of altering the pre- vs postnatal environments on a variety of metabolic, physiological and neuroendocrine functions, which lead to the development of offspring obesity, diabetes, hypertension and hyperlipidemia. During the gestational period, maternal malnutrition, obesity, type 1 and type 2 diabetes, and psychological and pharmacological stressors can all promote offspring obesity. Normal postnatal nutrition can sometimes reduce the adverse effect of some of these prenatal factors, but may also exacerbate the development of obesity and diabetes in offspring of dams that are malnourished during gestation. The genetic background of the individual is also an important determinant of outcome when the perinatal environment is perturbed. Individuals with an obesity-prone genotype are more likely to be adversely affected by factors such as maternal obesity and high-fat diets. Many perinatal manipulations are associated with reorganization of the central neural pathways which regulate food intake, energy expenditure and storage in ways that enhance the development of obesity and diabetes in offspring. Both leptin and insulin have strong neurotrophic properties so that an excess or an absence of either of them during the perinatal period may underlie some of these adverse developmental changes. As perinatal manipulations can permanently and adversely alter the systems that regulate energy homeostasis, it behooves us to gain a better understanding of the factors during this period that promote the development of offspring obesity as a means of stemming the tide of the emerging worldwide obesity epidemic.

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References

  1. Wang Y . Cross-national comparison of childhood obesity: the epidemic and the relationship between obesity and socioeconomic status. Int J Epidemiol 2001; 30: 1129–1136.

    Article  CAS  PubMed  Google Scholar 

  2. Kral JG, Biron S, Simard S, Hould FS, Lebel S, Marceau S et al. Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Pediatrics 2006; 118: e1644–e1649.

    Article  PubMed  Google Scholar 

  3. Ravelli GP, Stein ZA, Susser MW . Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 1976; 295: 349–353.

    Article  CAS  PubMed  Google Scholar 

  4. Enriori PJ, Evans AE, Sinnayah P, Jobst EE, Tonelli-Lemos L, Billes SK et al. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab 2007; 5: 181–194.

    Article  CAS  PubMed  Google Scholar 

  5. Koza RA, Nikonova L, Hogan J, Rim JS, Mendoza T, Faulk C et al. Changes in gene expression foreshadow diet-induced obesity in genetically identical mice. PLoS Genet 2006; 2: e81.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Waterland RA, Jirtle RL . Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 2003; 23: 5293–5300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004; 7: 847–854.

    Article  CAS  PubMed  Google Scholar 

  8. Reifsnyder PC, Churchill G, Leiter EH . Maternal environment and genotype interact to establish diabesity in mice. Genome Res 2000; 10: 1568–1578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gorski J, Dunn-Meynell AA, Hartman TG, Levin BE . Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance. Am J Physiol Regul Integr Comp Physiol 2006; 291: R768–R778.

    Article  CAS  PubMed  Google Scholar 

  10. Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE . Selective breeding for diet-induced obesity and resistance in Sprague–Dawley rats. Am J Physiol 1997; 273: R725–R730.

    CAS  PubMed  Google Scholar 

  11. Levin BE, Dunn-Meynell AA, Ricci MR, Cummings DE . Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. Am J Physiol 2003; 285: E949–E957.

    CAS  Google Scholar 

  12. Levin BE, Dunn-Meynell AA . Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats. Am J Physiol Regul Integr Comp Physiol 2000; 278: R231–R237.

    Article  CAS  PubMed  Google Scholar 

  13. Bouchard C, Perusse L . Genetics of obesity. Ann Rev Nutr 1993; 13: 337–354.

    Article  CAS  Google Scholar 

  14. Levin BE, Dunn-Meynell AA, McMinn JE, Cunningham-Bussel A, Chua Jr SC . A new obesity-prone, glucose intolerant rat strain (F.DIO). Am J Physiol Regul Integr Comp Physiol 2003; 285: R1184–R1191.

    Article  CAS  PubMed  Google Scholar 

  15. Bouret SG, Gorski JN, Patterson CM, Chen S, Levin BE, Simerly RB . Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab 2008; 7: 179–185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gorski JN, Dunn-Meynell AA, Levin BE . Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats. Am J Physiol Regul Integr Comp Physiol 2007; 292: R1782–R1791.

    Article  CAS  PubMed  Google Scholar 

  17. Levin BE, Dunn-Meynell AA . Reduced central leptin sensitivity in rats with diet-induced obesity. Am J Physiol 2002; 283: R941–R948.

    Article  Google Scholar 

  18. Levin BE, Dunn-Meynell AA, Banks WA . Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling prior to obesity onset. Am J Physiol Regul Integr Comp Physiol 2004; 286: R143–R150.

    Article  CAS  PubMed  Google Scholar 

  19. Irani BG, Dunn-Meynell AA, Levin BE . Altered hypothalamic leptin, insulin and melanocortin binding associated with moderate fat diet and predisposition to obesity. Endocrinology 2007; 148: 310–316.

    Article  CAS  PubMed  Google Scholar 

  20. Clegg DJ, Benoit SC, Reed JA, Woods SC, Levin BE . Reduced anorexic effects of insulin in obesity-prone rats and rats fed a moderate fat diet. Am J Physiol Regul Integr Comp Physiol 2005; 288: R981–R986.

    Article  CAS  PubMed  Google Scholar 

  21. Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA . Neuronal glucosensing: what do we know after 50 years? Diabetes 2004; 53: 2521–2528.

    Article  CAS  PubMed  Google Scholar 

  22. Jones AP, Friedman MI . Obesity and adipocyte abnormalities in offspring of rats undernourished during pregnancy. Science 1982; 215: 1518–1519.

    Article  CAS  PubMed  Google Scholar 

  23. Guo F, Jen KL . High-fat feeding during pregnancy and lactation affects offspring metabolism in rats. Physiol Behav 1995; 57: 681–686.

    Article  CAS  PubMed  Google Scholar 

  24. Levin BE, Govek E . Gestational obesity accentuates obesity in obesity-prone progeny. Am J Physiol 1998; 275: R1374–R1379.

    CAS  PubMed  Google Scholar 

  25. Guesnet P, Alasnier C, Alessandri JM, Durand G . Modifying the n-3 fatty acid content of the maternal diet to determine the requirements of the fetal and suckling rat. Lipids 1997; 32: 527–534.

    Article  CAS  PubMed  Google Scholar 

  26. Plagemann A, Harder T, Rake A, Janert U, Melchior K, Rohde W et al. Morphological alterations of hypothalamic nuclei due to intrahypothalamic hyperinsulinism in newborn rats. Int J Dev Neurosci 1999; 17: 37–44.

    Article  CAS  PubMed  Google Scholar 

  27. Flores MB, Fernandes MF, Ropelle ER, Faria MC, Ueno M, Velloso LA et al. Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats. Diabetes 2006; 55: 2554–2561.

    Article  CAS  PubMed  Google Scholar 

  28. Patterson CM, Dunn-meynell AA, Levin BE . Three weeks of early onset exercise prolongs obesity-resistance in DIO rats after exercise cessation. Am J Physiol Regul Integr Comp Physiol 2008; 294: R290–R301.

    Article  CAS  PubMed  Google Scholar 

  29. Applegate EA, Upton DE, Stern JS . Exercise and detraining: effect on food intake, adiposity and lipogenesis in Osborne–Mendel rats made obese by a high fat diet. J Nutr 1984; 114: 447–459.

    Article  CAS  PubMed  Google Scholar 

  30. Billington CJ, Briggs JE, Grace M, Levine AS . Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260: R321–R327.

    CAS  PubMed  Google Scholar 

  31. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997; 278: 135–138.

    Article  CAS  PubMed  Google Scholar 

  32. Butler AA, Marks DL, Fan W, Kuhn CM, Bartolome M, Cone RD . Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci 2001; 4: 605–611.

    Article  CAS  PubMed  Google Scholar 

  33. Levin BE, Kang L, Sanders NM, Dunn-Meynell AA . Role of neuronal glucosensing in the regulation of energy homeostasis. Diabetes 2006; 55: S122–S130.

    Article  CAS  Google Scholar 

  34. Baker RA, Herkenham M, Brady LS . Effects of long-term treatment with antidepressant drugs on proopiomelanocortin and neuropeptide Y mRNA expression in the hypothalamic arcuate nucleus in rats. J Neuroendocrinol 1996; 8: 337–343.

    Article  CAS  PubMed  Google Scholar 

  35. Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L et al. Serotonin activates the hypothalamic–pituitary–adrenal axis via serotonin 2C receptor stimulation. J Neurosci 2007; 27: 6956–6964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bouret SG, Draper SJ, Simerly RB . Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J Neurosci 2004; 24: 2797–2805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Grove KL, Smith MS . Ontogeny of the hypothalamic neuropeptide Y system. Physiol Behav 2003; 79: 47–63.

    Article  CAS  PubMed  Google Scholar 

  38. Levin BE, Dunn-Meynell AA . Maternal obesity alters adiposity and monoamine function in genetically predisposed offspring. Am J Physiol Regul Integr Comp Physiol 2002; 283: R1087–R1093.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Neurology Service, VA Medical Center, East Orange, Newark, NJ, USA

    B E Levin

  2. Department of Neurology and Neurosciences, New Jersey Medical School, Newark, NJ, USA

    B E Levin

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  1. B E Levin
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Correspondence to B E Levin.

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Levin, B. Synergy of nature and nurture in the development of childhood obesity. Int J Obes 33 (Suppl 1), S53–S56 (2009). https://doi.org/10.1038/ijo.2009.18

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