Developmental Origins of Obesity: Programming of Food Intake or Physical Activity?

  • David S. Gardner
  • Phillip Rhodes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 646)

Mans ability to capture, harness and store energy most efficiently as fat in adipose tissue has been an evolutionary success story for the majority of human existence. Only over the last 30–40 years has our remarkable metabolic efficiency been revealed as our energy balance increasingly favours storage without regular periods of depletion. Historical records show us that while the composition of our diet has changed markedly over this time, our overall energy intake has significantly reduced. The inevitable conclusion therefore is that habitual physical activity and thus energy expenditure has reduced by a greater extent. Recent studies have illustrated how the finely tuned long-term control of energy intake and of energy expenditure are both developmentally plastic and susceptible to environmentally-induced change that may persist with that individual throughout their adult life, invariably rendering them more susceptible to greater adipose tissue deposition. The central role that lean body mass has upon the ‘gating’ of energy sensing and the importance of regular physical activity for its potential to reduce the burden of a ‘thrifty phenotype’ will be briefly discussed in the present review.


Obesity physical activity nutrition appetite food intake programming 


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  1. Arany, Z., Lebrasseur, N., Morris, C., Smith, E., Yang, W., Ma, Y., Chin, S., & Spiegelman, B. M. (2007). The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 5, 35–46.PubMedCrossRefGoogle Scholar
  2. Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J., Funahashi, H., Williams, T., Ferreira, M., Tang, V., McGovern, R. A., Kenny, C. D., Christiansen, L. M., Edelstein, E., Choi, B., Boss, O., Aschkenasi, C., Zhang, C. Y., Mountjoy, K., Kishi, T., Elmquist, J. K., & Lowell, B. B. (2005). Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493–505.PubMedCrossRefGoogle Scholar
  3. Bedard, D., Shatenstein, B., & Nadon, S. (2004). Underreporting of energy intake from a self-administered food-frequency questionnaire completed by adults in Montreal. Public Health Nutr 7, 675–681.PubMedCrossRefGoogle Scholar
  4. Bouret, S. G. & Simerly, R. B. (2006). Developmental programming of hypothalamic feeding circuits. Clin Genet 70, 295–301.PubMedCrossRefGoogle Scholar
  5. Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004). Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 108–110.PubMedCrossRefGoogle Scholar
  6. Chakravarthy, M. V. & Booth, F. W. (2004). Eating, exercise, and “thrifty” genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 96, 3–10.PubMedCrossRefGoogle Scholar
  7. Cripps, R. L., Martin-Gronert, M. S., & Ozanne, S. E. (2005). Fetal and perinatal programming of appetite. Clin Sci (Lond) 109, 1–11.CrossRefGoogle Scholar
  8. Daniel, Z. C., Brameld, J. M., Craigon, J., Scollan, N. D., & Buttery, P. J. (2007). Effect of maternal dietary restriction during pregnancy on lamb carcass characteristics and muscle fiber composition. J Anim Sci 85, 1565–1576.PubMedCrossRefGoogle Scholar
  9. Daugaard, J. R., Nielsen, J. N., Kristiansen, S., Andersen, J. L., Hargreaves, M., & Richter, E. A. (2000). Fiber type-specific expression of GLUT4 in human skeletal muscle: influence of exercise training. Diabetes 49, 1092–1095.PubMedCrossRefGoogle Scholar
  10. Denton, J. C., Schultz, R., Jamurtas, A. Z., & Angelopoulos, T. J. (2004). Improvements in glucose tolerance in obese males with abnormal glucose tolerance following 10 days of aerobic exercise. Prev Med 38, 885–888.PubMedCrossRefGoogle Scholar
  11. Duehlmeier, R., Sammet, K., Widdel, A., von Engelhardt, W., Wernery, U., Kinne, J., & Sallmann, H. P. (2007). Distribution patterns of the glucose transporters GLUT4 and GLUT1 in skeletal muscles of rats (Rattus norvegicus), pigs (Sus scrofa), cows (Bos taurus), adult goats, goat kids (Capra hircus), and camels (Camelus dromedarius). Comp Biochem Physiol A Mol Integr Physiol 146, 274–282.PubMedCrossRefGoogle Scholar
  12. Enriori, P. J., Evans, A. E., Sinnayah, P., Jobst, E. E., Tonelli-Lemos, L., Billes, S. K., Glavas, M. M., Grayson, B. E., Perello, M., Nillni, E. A., Grove, K. L., & Cowley, M. A. (2007). Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab 5, 181–194.PubMedCrossRefGoogle Scholar
  13. Fahey, A. J., Brameld, J. M., Parr, T., & Buttery, P. J. (2005). The effect of maternal undernutrition before muscle differentiation on the muscle fiber development of the newborn lamb. J Anim Sci 83, 2564–2571.PubMedGoogle Scholar
  14. Food Standards Agency & Department of Health (2004). National Diet and Nutrition Survey: adults aged 19–64 years. Krebs, J. and Johnson, M. 5, 1–142. London, HMSO. Ref Type: Report.Google Scholar
  15. Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R., Elliott, K. S., Lango, H., Rayner, N. W., Shields, B., Harries, L. W., Barrett, J. C., Ellard, S., Groves, C. J., Knight, B., Patch, A. M., Ness, A. R., Ebrahim, S., Lawlor, D. A., Ring, S. M., Ben Shlomo, Y., Jarvelin, M. R., Sovio, U., Bennett, A. J., Melzer, D., Ferrucci, L., Loos, R. J., Barroso, I., Wareham, N. J., Karpe, F., Owen, K. R., Cardon, L. R., Walker, M., Hitman, G. A., Palmer, C. N., Doney, A. S., Morris, A. D., Davey-Smith, G., Hattersley, A. T., & McCarthy, M. I. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894.PubMedCrossRefGoogle Scholar
  16. Hardie, D. G., Hawley, S. A., & Scott, J. W. (2006). AMP-activated protein kinase – development of the energy sensor concept. J Physiol 574, 7–15.PubMedCrossRefGoogle Scholar
  17. Hood, D. A., Irrcher, I., Ljubicic, V., & Joseph, A. M. (2006). Coordination of metabolic plasticity in skeletal muscle. J Exp Biol 209, 2265–2275.PubMedCrossRefGoogle Scholar
  18. Horvath, T. L. & Bruning, J. C. (2006). Developmental programming of the hypothalamus: a matter of fat. Nat Med 12, 52–53.PubMedCrossRefGoogle Scholar
  19. Kalra, S. P., Dube, M. G., Pu, S., Xu, B., Horvath, T. L., & Kalra, P. S. (1999). Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrinol Rev 20, 68–100.CrossRefGoogle Scholar
  20. Keith, S. W., Redden, D. T., Katzmarzyk, P. T., Boggiano, M. M., Hanlon, E. C., Benca, R. M., Ruden, D., Pietrobelli, A., Barger, J. L., Fontaine, K. R., Wang, C., Aronne, L. J., Wright, S. M., Baskin, M., Dhurandhar, N. V., Lijoi, M. C., Grilo, C. M., Deluca, M., Westfall, A. O., & Allison, D. B. (2006). Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond) 30, 1585–1594.CrossRefGoogle Scholar
  21. Kimm, S. Y., Glynn, N. W., Obarzanek, E., Kriska, A. M., Daniels, S. R., Barton, B. A., & Liu, K. (2005). Relation between the changes in physical activity and body-mass index during adolescence: a multicentre longitudinal study. Lancet 366, 301–307.PubMedCrossRefGoogle Scholar
  22. Langley-Evans, S. C., Bellinger, L., & McMullen, S. (2005). Animal models of programming: early life influences on appetite and feeding behaviour. Matern Child Nutr 1, 142–148.PubMedCrossRefGoogle Scholar
  23. Levine, J. A., Lanningham-Foster, L. M., McCrady, S. K., Krizan, A. C., Olson, L. R., Kane, P. H., Jensen, M. D., & Clark, M. M. (2005). Interindividual variation in posture allocation: possible role in human obesity. Science 307, 584–586.PubMedCrossRefGoogle Scholar
  24. Lisboa, P. C., Passos, M. C., Dutra, S. C., Bonomo, I. T., Denolato, A. T., Reis, A. M., & Moura, E. G. (2006). Leptin and prolactin, but not corticosterone, modulate body weight and thyroid function in protein-malnourished lactating rats. Horm Metab Res 38, 295–299.PubMedCrossRefGoogle Scholar
  25. Lissner, L. (2002). Measuring food intake in studies of obesity. Public Health Nutr 5, 889–892.PubMedCrossRefGoogle Scholar
  26. Mallinson, J. E., Sculley, D. V., Craigon, J., Plant, R., Langley-Evans, S. C., & Brameld, J. M. (2007). Fetal exposure to a maternal low-protein diet during mid-gestation results in muscle-specific effects on fibre type composition in young rats. Brit J Nutr 98, 292–299.PubMedCrossRefGoogle Scholar
  27. Maltin, C. A., Delday, M. I., Sinclair, K. D., Steven, J., & Sneddon, A. A. (2001). Impact of manipulations of myogenesis in utero on the performance of adult skeletal muscle. Reproduction 122, 359–374.PubMedCrossRefGoogle Scholar
  28. Mark, A. L., Rahmouni, K., Correia, M., & Haynes, W. G. (2003). A leptin-sympathetic-leptin feedback loop: potential implications for regulation of arterial pressure and body fat. Acta Physiol Scand 177, 345–349.PubMedCrossRefGoogle Scholar
  29. Miralles, O., Sanchez, J., Palou, A., & Pico, C. (2006). A physiological role of breast milk leptin in body weight control in developing infants. Obesity (Silver.Spring) 14, 1371–1377.CrossRefGoogle Scholar
  30. Mortensen, O. H., Frandsen, L., Schjerling, P., Nishimura, E., & Grunnet, N. (2006). PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype. Am J Physiol Endocrinol Metab 291, E807–E816.PubMedCrossRefGoogle Scholar
  31. Mostyn, A., Sebert, S., Litten, J. C., Perkins, K. S., Laws, J., Symonds, M. E., & Clarke, L. (2006). Influence of porcine genotype on the abundance of thyroid hormones and leptin in sow milk and its impact on growth, metabolism and expression of key adipose tissue genes in offspring. J Endocrinol 190, 631–639.PubMedCrossRefGoogle Scholar
  32. Muhlhausler, B. S., Adam, C. L., Findlay, P. A., Duffield, J. A., & McMillen, I. C. (2006). Increased maternal nutrition alters development of the appetite-regulating network in the brain. FASEB J 20, 1257–1259.PubMedCrossRefGoogle Scholar
  33. Nassis, G. P., Papantakou, K., Skenderi, K., Triandafillopoulou, M., Kavouras, S. A., Yannakoulia, M., Chrousos, G. P., & Sidossis, L. S. (2005). Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls. Metabolism 54, 1472–1479.PubMedCrossRefGoogle Scholar
  34. National Food Survey (2007). Household food expenditure and consumption and nutrient intake 1974–2007. DEFRA/ONS (2007) Expenditure and Food Survey. TSO, London. https://statistics.
  35. Olefsky, J. M. (1999). Insulin-stimulated glucose transport minireview series. J Biol Chem 274, 1863.PubMedCrossRefGoogle Scholar
  36. Oscai, L. B. & McGarr, J. A. (1978). Evidence that the amount of food consumed in early life fixes appetite in the rat. Am J Physiol 235, R141–R144.PubMedGoogle Scholar
  37. Ozanne, S. E., Jensen, C. B., Tingey, K. J., Storgaard, H., Madsbad, S., & Vaag, A. A. (2005). Low birth weight is associated with specific changes in muscle insulin signaling protein expression. Diabetologia 48, 547–552.PubMedCrossRefGoogle Scholar
  38. Popkin, B. M. (2006). Global nutrition dynamics: the world is shifting rapidly toward a diet linked with noncommunicable diseases. Am J Clin Nutr 84, 289–298.PubMedGoogle Scholar
  39. Prentice, A. M. & Jebb, S. A. (2003). Fast foods, energy density and obesity: a possible mechanistic link. Obes Rev 4, 187–194.PubMedCrossRefGoogle Scholar
  40. Prynne, C. J., Paul, A. A., Price, G. M., Day, K. C., Hilder, W. S., & Wadsworth, M. E. (1999). Food and nutrient intake of a national sample of 4-year-old children in 1950: comparison with the 1990s. Public Health Nutr 2, 537–547.PubMedCrossRefGoogle Scholar
  41. Roden, M. (2005). Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes. Int J Obes (Lond) 29(Suppl 2), S111–S115.CrossRefGoogle Scholar
  42. Savino, F., Liguori, S. A., Oggero, R., Silvestro, L., & Miniero, R. (2006). Maternal BMI and serum leptin concentration of infants in the first year of life. Acta Paediatr 95, 414–418.PubMedCrossRefGoogle Scholar
  43. Smyth, S. & Heron, A. (2006). Diabetes and obesity: the twin epidemics. Nat Med 12, 75–80.PubMedCrossRefGoogle Scholar
  44. Sothern, M. S. (2004). Obesity prevention in children: physical activity and nutrition. Nutrition 20, 704–708.PubMedCrossRefGoogle Scholar
  45. Swinburn, B. & Egger, G. (2004). The runaway weight gain train: too many accelerators, not enough brakes. BMJ 329, 736–739.PubMedCrossRefGoogle Scholar
  46. Vickers, M. H., Breier, B. H., Cutfield, W. S., Hofman, P. L., & Gluckman, P. D. (2000). Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 279, E83–E87.PubMedGoogle Scholar
  47. Vickers, M. H., Breier, B. H., McCarthy, D., & Gluckman, P. D. (2003). Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hyperca-loric nutrition. Am J Physiol Regul Integr Comp Physiol 285, R271–R273.PubMedGoogle Scholar
  48. Vickers, M. H., Gluckman, P. D., Coveny, A. H., Hofman, P. L., Cutfield, W. S., Gertler, A., Breier, B. H., & Harris, M. (2005). Neonatal leptin treatment reverses developmental programming. Endocrinology 146, 4211–4216.PubMedCrossRefGoogle Scholar
  49. Widdowson, E. M. (1970). Harmony of growth. Lancet 1, 902–905.PubMedGoogle Scholar
  50. Widdowson, E. M. & McCance, R. A. (1975). A review: new thoughts on growth. Pediatr Res 9, 154–156.PubMedCrossRefGoogle Scholar
  51. Wilkin, T. J., Mallam, K. M., Metcalf, B. S., Jeffery, A. N., & Voss, L. D. (2006). Variation in physical activity lies with the child, not his environment: evidence for an ‘activitystat’ in young children (EarlyBird 16). Int J Obes (Lond) 30, 1050–1055.CrossRefGoogle Scholar
  52. Williams, P. J., Kurlak, L. O., Perkins, A. C., Budge, H., Stephenson, T., Keisler, D., Symonds, M. E., & Gardner, D. S. (2007). Hypertension and impaired renal function accompany juvenile obesity: the effect of prenatal diet. Kidney Int 72(3), 279–289.PubMedCrossRefGoogle Scholar
  53. Wisloff, U., Najjar, S. M., Ellingsen, O., Haram, P. M., Swoap, S., Al Share, Q., Fernstrom, M., Rezaei, K., Lee, S. J., Koch, L. G., & Britton, S. L. (2005). Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science 307, 418–420.PubMedCrossRefGoogle Scholar
  54. Zhu, M. J., Ford, S. P., Means, W. J., Hess, B. W., Nathanielsz, P. W., & Du, M. (2006). Maternal nutrient restriction affects properties of skeletal muscle in offspring. J Physiol 575, 241–250.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2009

Authors and Affiliations

  1. 1.Centre for Reproduction and Early Life, Institute of Clinical ResearchUniversity HospitalNottinghamUK

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