Nutrition, Behavior, and the Developmental Origins of the Metabolic Syndrome

  • Jared Edward Reser


It is clear that the modern epidemic of obesity, cardiovascular disease, diabetes mellitus, and associated comorbidities is largely a product of our modern environment. Artificially high levels of sugars, fats, and processed foods, along with sedentary behavior constitute an “obesogenic” environment which makes us more susceptible to the metabolic syndrome today than our foraging ancestors were millennia ago. A number of comparative analyses relevant to the influence of behavior, diet, and nutrition on the metabolic syndrome are reviewed here, especially with regard to the developmental origins of the syndrome. It has become clear that early environmental conditions, particularly poor nutrition, have the ability to act as cues that program the phenotype in utero. It is thought that the fetus has an adaptive ability to perceive nutritional deprivation, and reprogram its metabolic systems for energy efficiency, as a predictive response to expected environmental scarcity. These metabolic alterations are thought to be beneficial in times of poor nutritional quality, but unfortunately have consistently been shown to result in adverse health outcomes and metabolic disease, when food is calorie dense and readily available. These early life changes are brought about by alterations in cellular proliferation and differentiation that are ultimately driven by neuroendocrine, cellular, and epigenetic adaptations to undernutrition. Besides the various metabolic changes, animals programmed for thrift have been shown to exhibit neurological changes resulting in hyperphagia, increased sedentariness, and volume reductions in the cerebral cortex. A great deal of evidence, including countless animal studies and a worldwide series of epidemiological investigations, has supported the close relationship between early nutritional status and susceptibility to the major risk factors (increased adiposity, hypertension, and insulin resistance) for the metabolic syndrome in later life. The perspectives originated by James Neel (the thrifty genotype hypothesis), and David Barker (the thrifty phenotype hypothesis) have remained important interpretations through which to view the nature of the genetic, structural, and adaptive facets of the programming of metabolic function. Moreover, these perspectives, and the integrative conceptualizations that they promote, have begun to provide valuable direction for research and health care.


Insulin Resistance Metabolic Syndrome Sedentary Behavior Lactase Persistence Nutritional Deprivation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Low density lipoprotein


Fetal origins of adult disease


  1. Barbazanges A, Piazza PV, Le Moal M, Maccari S. J Neurosci. 1996;16:3943–9.PubMedGoogle Scholar
  2. Barker DJP. Fetal Maternal Med Rev. 1994;6:71–80.CrossRefGoogle Scholar
  3. Barker DJP. Mothers, babies and health in later life. London: Churchill Livingstone; 1998.Google Scholar
  4. Barker D, Eriksson J, Forsen T, Osmond C. Int J Epidemiol. 2002;31:1235–9.PubMedCrossRefGoogle Scholar
  5. Bateson P, Barker D, Clutton-Brock T, Deb D, D’Udine B, Foley R, Gluckman P, Godfrey K, Kirkwood T, Mirazon Lahr M, McNamara J, Metcalfe N, Monaghan P, Spencer H, Sultan S. Nature 2004;430:419–21.PubMedCrossRefGoogle Scholar
  6. Cettour-Rose P, Samec S, Russell AP, Summermatter S, Mainieri D, Carrillo-Theander C. Diabetes 2005;54:751–6.PubMedCrossRefGoogle Scholar
  7. Coleman D. Science 1979;203:663–5.PubMedCrossRefGoogle Scholar
  8. Crespi EJ, Denver RJ. Am J Hum Biol. 2005;17:44–54.PubMedCrossRefGoogle Scholar
  9. Desai M, Crowther NJ, Ozanne SE, Lucas A, Hales CN. Biochem SocTrans. 1995;23:31–5.Google Scholar
  10. Diamond J. Nature2003;423:599–602.PubMedCrossRefGoogle Scholar
  11. Dowse GK, Zimmet PZ, King H. Diabetes Care. 1991;14:968–74.PubMedCrossRefGoogle Scholar
  12. Drake AJ, Walker BR. J Endocrinol. 2004;180:1–16.PubMedCrossRefGoogle Scholar
  13. Eriksson J, Forsen T, Tuomilehto J, Osmond C, Barker D. Br Med J. 2001;322:949–53.CrossRefGoogle Scholar
  14. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486–97.Google Scholar
  15. Flier JS. J Clin Endocrinol Metab. 1998;83:1407–13.PubMedCrossRefGoogle Scholar
  16. Ford ES, Giles WH, Dietz WH. JAMA 2002;287:356–9.PubMedCrossRefGoogle Scholar
  17. Francis D, Diorio J, LaPlante P, Weaver S, Seckl JR, Meaney MJ. Ann NY Acad Sci. 1996;794:136–52.PubMedCrossRefGoogle Scholar
  18. Gluckman P, Hanson M. Trends Endocrinol Metab. 2004;15:183–7.Google Scholar
  19. Haines H, Hackel D, Schmidt-Nielsen K. Am J Physiol. 1965;208:297–300.PubMedGoogle Scholar
  20. Hales CN, Barker DJ. Diabetologia 1992;35:595–601.PubMedCrossRefGoogle Scholar
  21. Hales CN, Barker DJ. Br Med Bull. 2001;60:5–20.PubMedCrossRefGoogle Scholar
  22. Hanson MA, Gluckman PD. Basic Clin Pharmacol. 2008;102:90–3.CrossRefGoogle Scholar
  23. Harding, JE. Int J Epidemiol. 2001;30:15–23.PubMedCrossRefGoogle Scholar
  24. Kensara OA, Wootton SA, Phillips DI, Patel M, Jackson AA, Elia M. Am J Clin Nutr. 2005;82:980–7.PubMedGoogle Scholar
  25. Langley-Evans SC. J Hypertens.1997;15:537–44.PubMedCrossRefGoogle Scholar
  26. Langley SC, Jackson AA. Clin Sci. 1994;86:217–22.PubMedGoogle Scholar
  27. Law CM, Shiell AW. J Hypertens. 1996;14:935–41.PubMedCrossRefGoogle Scholar
  28. McKeigue P. In: Kuh D, Ben-Shlomo Y, editors. A life course approach to chronic disease epidemiology. Oxford: Oxford University Press; 1997. p. 78–100.Google Scholar
  29. Neel JV. Am J Hum Genet. 1962;14:353–62.PubMedGoogle Scholar
  30. Neel JV. In: Kobberling J, Tattersall R, editors. The genetics of diabetes mellitus. Amsterdam: Academic; 1982. p. 137–47.Google Scholar
  31. Neel JV. Nutr Rev. 1999;57:2–9.CrossRefGoogle Scholar
  32. Nesse R, Williams G. Sci Am. 1998;279:58–65.CrossRefGoogle Scholar
  33. Ozanne SE, Hales CN. Nature 2004;427:411–2.PubMedCrossRefGoogle Scholar
  34. Petry CJ, Ozanne SE, Wang CL, Hales CN. Clin Sci Lond. 1997;93:147–52.PubMedGoogle Scholar
  35. Phillips DI. Diabetes Care. 1998;21:150–5.Google Scholar
  36. Pollard TM. Western diseases: an evolutionary perspective. Cambridge UK: Cambridge University Press; 2008. p. 5–9.Google Scholar
  37. Ravelli, GP, Stein ZA, Susser MW. N Engl J Med. 1976;295:349–53.PubMedCrossRefGoogle Scholar
  38. Reser JE. Med Hypotheses. 2006;67:529–44.PubMedCrossRefGoogle Scholar
  39. Ridley M. Nature via nurture: genes experience and what makes us human. New York: Harper Collins; 2003.Google Scholar
  40. Scott EM, Grant PJ. Diabetologia 2006;49:1462–6.PubMedCrossRefGoogle Scholar
  41. Schulz LO, Bennett PH, Ravussin E, Kidd JR, Kidd KK. Diabetes Care. 2006;29:1866–71.PubMedCrossRefGoogle Scholar
  42. Schwartz MW, Dallman MF, Woods SC. Am J Physiol. 1995;269:949–57.Google Scholar
  43. Siemelink M, Verhoef A, Dormans JA, Span PN, Piersma AH. Diabetologia 2002;45:1397–403.PubMedCrossRefGoogle Scholar
  44. Tolsa CB, Zimine S, Warfield SK, Freschi M, Rossignol AS, Lazeyras F, Hanquinet S, Pfizenmaier M, Huppi PS. Pediat Res. 2004;56:131–8.CrossRefGoogle Scholar
  45. Valencia M, Bennett P, Ravussin E, Esparza J, Fox C, Schulz L. Nutr Rev. 1999;57:55–7.CrossRefGoogle Scholar
  46. Via S, Lande R. Evolution 1985;39:505–22.CrossRefGoogle Scholar
  47. Vickers MH, Breier BH, McCarthy D, Gluckman PD. Am J Physiol Endocrinol Metab. 2000;279:83–7.Google Scholar
  48. Wells J. J Theor Biol. 2003;7:221:143–61.CrossRefGoogle Scholar
  49. Zhang T, Parent C, Weaver I, Meaney M. Ann NY Acad Sci.2004;1032:85–103.PubMedCrossRefGoogle Scholar
  50. Zimmet P. In: Fischer E, Moller G, editors. The medical challenge: complex traits. Munich: Piper; 1997. p. 55–110.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Psychology DepartmentUniversity of Southern CaliforniaLos AngelesUSA

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