Early Nutrition and Later Obesity: Animal Models Provide Insights into Mechanisms

  • Cornelia C. Metges
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 646)

Epidemiological evidence suggests that in utero as well as early postnatal life exposure to an imbalanced nutrition are both related to a greater propensity to become obese in later life. Rodent and sheep models of metabolic programming of obesity by early life nutrition include maternal low and high dietary protein and energy or food intake as well as high fat diets. Maternal nutritional imbalance during pregnancy and/or lactation programs energy expenditure, food intake and physical activity in the offspring. Underlying mechanisms of altered energy balance in programmed offspring are associated with disturbances of ontogeny of hypothalamic feeding circuits, leptin and glucocorticoid action which have long-lasting effects on food intake, energy expenditure and fat tissue metabolism.


Metabolic programming obesity animal model leptin glucocorticoids 


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  1. Andreasyan, K., A.L. Ponsonby, T. Dwyer, R. Morley, M. Riley, K. Dear and J. Cochrane (2007). Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth. Eur J Clin Nutr 61: 498–508.PubMedGoogle Scholar
  2. Anguita, R.M., D.M. Sigulem and A.L. Sawaya (1993). Intrauterine food restriction is associated with obesity in young rats. J Nutr 123: 1421–1428.PubMedGoogle Scholar
  3. Armitage, J.A., I.Y. Khan, P.D. Taylor, P. Nathanielsz and L. Poston (2004). Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol 561(2): 355–377.PubMedCrossRefGoogle Scholar
  4. Armitage, J.A., P.D. Taylor and L. Poston (2005). Experimental models of developmental programming: consequences of exposure to an energy rich diet during development. J Physiol 565(1): 3–8.PubMedCrossRefGoogle Scholar
  5. Ashworth, C.J., N. Hoggard, L. Thomas, J.G. Mercer, J.M. Wallace and R.G. Lea (2000). Placental leptin. Rev Reprod 5: 18–24.PubMedCrossRefGoogle Scholar
  6. Bayol, S.A., B.H. Simbi and N.C. Stickland (2005). A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning. J Physiol 567(Pt 3): 951–961.PubMedCrossRefGoogle Scholar
  7. Bellinger, L., D.V. Sculley and S.C. Langley-Evans (2006). Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats. Int J Obes 30: 729–738.CrossRefGoogle Scholar
  8. Bertram, C., A.R. Trowern, N. Copin, A.A. Jackson and C.B. Whorwood (2001). The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142: 2841–2853.PubMedCrossRefGoogle Scholar
  9. Boney, C.M, A. Verma, R.Tucker and B.R. Vohr (2005). Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115: e290–e296.PubMedCrossRefGoogle Scholar
  10. Boullo-Ciocca, S., A. Dutour, V. Guillaume, V. Achard, C. Oliver and M. Grino (2005). Postnatal diet-induced obesity in rats upregulates systemic and adipose tissue glucocorticoid metabolism during development and adulthood: its relationship with the metabolic syndrome. Diabetologia 54: 197–203.Google Scholar
  11. Buckley, A.J., A.L. Jaquiery and J.E. Harding (2005a). Nutritional programming of adult disease. Cell Tissue Res 322: 73–79.CrossRefGoogle Scholar
  12. Buckley, A.J., B. Keseru, J. Briody, M. Thompson, S.E. Ozanne and C.H. Thompson (2005b). Altered body composition and metabolism in the male offspring of high fat-fed rats. Metabolism 54: 500–507.CrossRefGoogle Scholar
  13. Cherala, G., B.H. Shapiro and A.P. D'mello (2006). Two low protein diets differentially affect food consumption in pregnant and lactating rats and long-term growth in their offspring. J Nutr 136: 2827–2833.PubMedGoogle Scholar
  14. Clancy, B., R.B. Darlington and B.L. Finlay (2001). Translating developmental time across mammalian species. Neuroscience 105: 7–17.PubMedCrossRefGoogle Scholar
  15. Dorner, G. and A. Plagemann (1994). Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Horm Metab Res 26: 213–21.PubMedCrossRefGoogle Scholar
  16. Daenzer, M., S. Ortmann, S. Klaus and C.C. Metges (2002). Prenatal high protein exposure decreases energy expenditure and increases adiposity in young rats. J Nutr 132: 142–144.PubMedGoogle Scholar
  17. Gluckman, P.D. and M.A. Hanson (2004). The developmental origins of the metabolic syndrome. Trends Endocrinol Metab 15: 183–187.PubMedCrossRefGoogle Scholar
  18. Gnanalingham, M.G., A. Mostyn, M.E. Symonds and T. Stephenson (2005). Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein 2. Am J Physiol Regul 289: 1407–1415.Google Scholar
  19. Grove, K.L. and M.A. Cowley (2005). Is ghrelin a signal for the development of metabolic systems? J Clin Invest 115: 3393–3397.PubMedCrossRefGoogle Scholar
  20. Hales, C.N. and D. J. Barker (1992). Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35: 595–601.PubMedCrossRefGoogle Scholar
  21. Keith, S.W., D.T. Redden, P.T. Katzmarzyk, M.M. Bogganio, E.C. Hanlon, R.M. Benca, D. Ruden, A. Pietrobelli, J.L. Barger, C. Wang et al. (2006). Putative contributors to the secular increase in obesity: exploring the roads less travelled. Int J Obes 30: 1585–1594.CrossRefGoogle Scholar
  22. Kensara, O.A., S.A. Wootton, D.I. Phillips, M. Patel, A.A. Jackson and M. Elia (2005). Fetal programming of body composition: relation between birth weight and body composition measured by dual x-ray absorptiometry and anthropometric methods in older Englishmen. Am J Clin Nutr 82: 980–987.PubMedGoogle Scholar
  23. Khan, I.Y., P.D. Tylor, V. Dekou, P.T. Seed, L. Lakasing, D. Graham et al. (2003). Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 41: 168–175.PubMedCrossRefGoogle Scholar
  24. Langley-Evans, S.C. (2000). Critical differences between two low protein diet protocols in the programming of hypertension in rats. Int J Food Sci Nutr 51: 11–17.PubMedCrossRefGoogle Scholar
  25. Levin, B.E. and E. Govek (1998). Gestational obesity accentuates obesity in obesity-prone progeny. Am J Physiol Regul 275: R1375–R1379.Google Scholar
  26. Metges, C.C. and H.M. Hammon (2005). Nutritional programming: prenatal nutritional effects on the regulation of growth and metabolism. J Anim Feed Sci 14(Suppl. 1): 15–30.Google Scholar
  27. Okosun, I.S., Y. Liao, C.N. Rotimi, G.E. Dever and R.S. Cooper (2000). Impact of birth weight in ethnic variations in subcutaneous and central adiposity in American children aged 5–11 Years. Int J Obes Relat Metab Disord 24: 479–484.PubMedCrossRefGoogle Scholar
  28. Ong, K.K. (2006). Size at birth, postnatal growth and risk of obesity. Horm Res 65 (Suppl. 3): 65–69.PubMedCrossRefGoogle Scholar
  29. Ong, K.K., M.L. Ahmed, P.M. Emmett, M.A. Preece, D.B. Dunger and Avon Longitudinal study of pregnancy and childhood study team (2000). Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. Brit Med J 320: 967–971.PubMedCrossRefGoogle Scholar
  30. Owen, C.G., R.M. Martin, P.H. Whincup, G.D. Smith and D.G. Cook (2005). Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics 115: 1367–1377.PubMedCrossRefGoogle Scholar
  31. Ozaki, T., H. Nishina, A. Hanson and L. Poston (2001). Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol 530: 141–152.PubMedCrossRefGoogle Scholar
  32. Ozanne, S.E. and C.N. Hales (2004). Lifespan: catch-up growth and obesity in male mice. Nature 427(6973): 411–412.PubMedCrossRefGoogle Scholar
  33. Petry, C.J., S.E. Ozanne, C.L. Wang and C.N. Hales (1997). Early protein restriction and obesity independently induce hypertension in 1-Year-old rats. Clin Sci (Lond) 93: 147–152.Google Scholar
  34. Sarandakou, A., E. Protonotariou, D. Rizos, A. Malamitsi-Puchner, G. Giannaki, I. Phocas and G. Creatsas (2000). Serum leptin concentrations during perinatal period. Am J Perinatol 17: 325–328.PubMedCrossRefGoogle Scholar
  35. Stettler, N., V.A. Stallings, A.B. Troxel, J. Zhao, R. Schinnar, S.E. Nelson et al. (2005). Weight gain in the first week and life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation 111: 1897–1903.PubMedCrossRefGoogle Scholar
  36. Stocker, C., J. O'Dowd, N.M. Morton, E. Wargent, M.V. Sennitt, D. Hislop, S. Glund, J.R. Seckl, J.R.S. Arch and M.A. Cawthorne (2004). Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mother with leptin during pregnancy and lactation. Int J Obes 28: 129–136.CrossRefGoogle Scholar
  37. Symonds, M.E., A. Mostyn, S. Pearce, H. Budge and T. Stephenson (2003). Endocrine and nutritional regulation of fetal adipose tissue development. J Endocrinol 179: 293–299.PubMedCrossRefGoogle Scholar
  38. Symonds, M.E., S. Pearce, J. Bispham, D.S. Gardner and T. Stephenson (2004). Timing of nutrient restriction and programming of fetal adipose tissue development. Proc Nutr Soc 63: 397–403.PubMedCrossRefGoogle Scholar
  39. Thone-Reineke, C., P. Kalk, M. Dorn, S. Klaus, K. Simon, T. Pfab, M. Godes, P. Persson, T. Unger and B. Hocher (2006). High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner. Am J Physiol Regul 291: R1025–R1030.Google Scholar
  40. Vickers, M.H., B.H. Breier, W.S. Cutfield, P.L. Hofman and P.D. Gluckman (2000). Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 279: E83–E87.PubMedGoogle Scholar
  41. Vickers, M.H., B.H. Breier, D. McCarthy and P.D. Gluckman (2003). Sedentary behaviour during postnatal life is determined by the prenatal environment and exacerbated by postnatal hyper-caloric nutrition. Am J Physiol Regul 285: R271–R273.Google Scholar
  42. Vickers, M.H., P.D. Gluckman, A.H. Coveny, P.L. Hofman, W.S. Cutfield, A. Gertler, B.H. Breier and M. Harris (2005). Neonatal leptin treatment reverses developmental programming. Endocrinology 146: 4211–4216.PubMedCrossRefGoogle Scholar
  43. Walker, B.R. (2007). Extra-adrenal regeneration of glucocorticoids by 11²-hydroxysteroid dehy-drogenase type 1: physiological regulator and pharmacological target for energy partitioning. Proc Nutr Soc 66: 1–8.PubMedCrossRefGoogle Scholar
  44. Wallace, J.M., R.P. Aitken, J.S. Milne and W.W. Hay (2004). Nutritionally mediated placental growth restriction in the growing adolescent: consequences for the fetus. Biol Reprod 71: 1055–1062.PubMedCrossRefGoogle Scholar
  45. Watson, R.E., J.M. DeSesso, M.E. Hurtt and G.D. Cappon (2006). Postnatal growth and morphological development of the brain: a species comparison. Birth Def Res (Part B) 77: 471–484.CrossRefGoogle Scholar
  46. Westerterp-Platenga, M.S. (2003). The significance of protein in food intake and body weight regulation. Curr Opin Clin Nutr Metab Care 6: 635–638.CrossRefGoogle Scholar
  47. Yura, S., H. Itoh, N. Sagawa, H. Yamamoto, H. Masuzaki, K. Nakao, M. Kawamura, M. Takemura, K. Kakui, Y. Ogawa and S. Fujii (2005). Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab 1: 371–378.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2009

Authors and Affiliations

  1. 1.Research unit ‘Nutritional Physiology’Research Institute of Farm Animal BiologyDummerstorfGermany

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