Excess bodyweight is the sixth most important risk factor contributing to the overall burden of disease worldwide. In excess of a billion adults and 10% of all children are now classified as overweight or obese. The main adverse consequences of obesity are the metabolic syndrome, cardiovascular disease and type 2 diabetes and a diminished average life expectancy. It has been argued that the complex pathological processes underlying obesity reflect environmental and genetic interactions, and individuals from disadvantaged communities seem to have greater risks than more affluent individuals partly because of fetal and postnatal programming interactions. Abundant evidence indicates that the obesity epidemic reflects progressive secular and age-related decreases in physical activity, together with passive over-consumption of energy dense foods despite neurobiological processes designed to regulate energy balance. The difficulty in treating obesity, however, highlights the deficits in our current understanding of the pathophysiology which underlies the initiation and chronic nature of this disorder. Large population based studies in Europe and North America in healthy women and in women with gestational diabetes have demonstrated that there are clear relationships between maternal and fetal nutrient supply, fetal growth patterns and the subsequent risk of obesity and glucose intolerance in childhood and adult life. In this review we discuss the impact of fetal nutrition on the biology of the developing adipocyte and brain and the growing evidence base supporting an intergenerational cycle of obesity.
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References
Bouret, S. G., Draper, S. J., and Simerly, R. B. (2004). Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304:108–110.
Catalano, P. M., Kirwan, J. P., Haugel-de Mouzon, S., and King, J. (2003). Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus. J Nutr 133:1674S–1683S.
Curhan, G. C., Chertow, G. M., Willett, W. C., Spiegelman, D., Colditz, G. A., Manson, J. E., Speizer, F. E., and Stampfer, M. J. (1996a). Birth weight and adult hypertension and obesity in women. Circulation 94:1310–1315.
Curhan, G. C., Willett, W. C., Rimm, E. B., Spiegelman, D., Ascherio, A. L., and Stampfer, M. J. (1996b). Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 94:3246–3250.
Davidowa, H. and Plagemann, A. (2000a). Decreased inhibition by leptin of hypothalamic arcuate neurons in neonatally overfed young rats. Neuroreport 11:2795–2798.
Davidowa, H. and Plagemann, A. (2000b). Different responses of ventromedial hypothalamic neurons to leptin in normal and early postnatally overfed rats. Neurosci Lett 293:21–24.
Davidowa, H. and Plagemann, A. (2001). Inhibition by insulin of hypothalamic VMN neurons in rats overweight due to postnatal overfeeding. Neuroreport 12:3201–3204.
Davidowa, H., Li, Y., and Plagemann, A. (2003). Altered responses to orexigenic (AGRP, MCH) and anorexigenic (alpha-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats. Eur J Neurosci 18:613–621.
Ekelund, U., Ong, K., Linne, Y., Neovius, M., Brage, S., Dunger, D. B., Wareham, N. J., and Rossner, S. (2006). Upward weight percentile crossing in infancy and early childhood independently predicts fat mass in young adults: the Stockholm Weight Development Study (SWEDES). Am J Clin Nutr 83:324–330.
Fall, C. H., Osmond, C., Barker, D. J., Clark, P. M., Hales, C. N., Stirling, Y., and Meade, T. W. (1995). Fetal and infant growth and cardiovascular risk factors in women. BMJ 310:428–432.
Flegal, K. M., Carroll, M. D., Ogden, C. L., and Johnson, C. L. (2002). Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288:1723–1727.
Galtier-Dereure, F., Boegner, C., and Bringer, J. (2000). Obesity and pregnancy: complications and cost. Am J Clin Nutr 71:1242S–1248S.
Jensen, D. M., Damm, P., Sorensen, B., Molsted-Pedersen, L., Westergaard, J. G., and Ovesen, P.-H. (2003). Pregnancy outcomes and prepregnancy body mass index is 2459 glucose-tolerant Danish women. Am J Obstet Gynecol 189:239–244.
LaCoursiere, D. Y., Bloebaum, L., Douncan, J. D., and Varner, M. W. (2005). Population-based trends and correlates of maternal overweight and obesity, Utah 1991–2001. Am J Obstet Gynecol 192:832–839.
Maffeis, C., Micciolo, R., Must, A., Zaffanello, M., and Pineli, L. (1994). Parental and perinatal factors associated with childhood obesity in north-east Italy. Int J Obes Relat Metab Disord 18:301–305.
Muhlhausler, B. S., McMillen, I. C., Rouzaud, G., Findlay, P. A., Marrocco, E. M., Rhind, S. M., and Adam, C. L. (2004). Appetite regulatory neuropeptides are expressed in the sheep hypoth-alamus before birth. J Neuroendocrinol 16:502–507.
Muhlhausler, B. S., Adam, C. L., Marrocco, E. M., Findlay, P. A., Roberts, C. T., McFarlane, J. R., Kauter, K. G., and McMillen, I. C. (2005). Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. J Physiol 565:185–195.
Muhlhausler, B. S., Adam, C. L., Findlay, P. A., Duffield, J. A., and McMillen, I. C. (2006). Increased maternal nutrition alters development of the appetite-regulating network in the brain. FASEB J 20:1257–1259.
Muhlhausler, B. S., Duffield, J. A., and McMillen, I. C. (2007). Increased maternal nutrition stimulates peroxisome proliferator activated receptor-y (PPARy), adiponectin and leptin mRNA expression in adipose tissue before birth. Endocrinology 148:878–885.
Ogden, C. L., Carroll, M. D., Curtin, L. R., McDowell, M. A., Tabak, C. J., and Flegal, K. M. (2006). Prevalence of overweight and obesity in the United states, 1999–2004. JAMA 295:1549–1555.
Oken, E. and Gillman, M. W. (2003). Fetal origins of obesity. Obes Res 11:496–506.
Ong, K. K., Emmett, P. M., Noble, S., Ness, A., and Dunger, D. B. (2006). Dietary energy intake at the age of 4 months predicts postnatal weight gain and childhood body mass index. Pediatrics 117:e503–e508.
Parsons, T. J., Power, C., and Manor, O. (2001). Fetal and early life growth and body mass index from birth to early adulthood in 1958 British cohort: longitudinal study. BMJ 323:1331–1335.
Rugholm, S., Baker, J. L., Olsen, L. W., Schack-Nielsen, L., Bua, J., and Sorensen, T. I. A. (2005). Stability of the association between birth weight and childhood overweight during the development of the obesity epidemic. Obes Res 13:2187–2194.
Semple, R. K., Chatterjee, V. K., and O'Rahilly, S. (2006). PPAR gamma and human metabolic disease. J Clin Invest 116:581–589.
Silverman, B. L., Rizzo, T., Green, O. C., Cho, N. H., Winter, R. J., Ogata, E. S., Richards, G. E., and Metzger, B. E. (1991). Long-term prospective evaluation of offspring of diabetic mothers. Diabetes 40:121–125.
Stettler, N., Zemel, B. S., Kumanyika, S., and Stallings, V. A. (2002). Infant weight gain and childhood overweight status in a multicenter, cohort study. Pediatrics 109:194–199.
Stettler, N., Kumanyika, S. K., Katz, S. H., Zemel, B. S., and Stallings, V. A. (2003). Rapid weight gain during infancy and obesity in young adulthood in a cohort of African Americans.Am J Clin Nutr 77:1374–1378.
Stettler, N., Stallings, V. A., Troxel, A. B., Zhao, J., Schinnar, R., Nelson, S. E., Ziegler, E. E., and Strom, B. L. (2005). Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation 111:1897–1903.
Warnes, K. E., Morris, M. J., Symonds, M. E., Phillips, I. D., Clarke, I. J., Owens, J. A., and McMillen, I. C. (1998). Impact of gestational age, cortisol and maternal undernutrition on hypothalamic neuropeptide Y expression in the sheep fetus. J Neuroendocrinol 10:51–57.
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McMillen, I.C. et al. (2009). The Early Origins of Later Obesity: Pathways and Mechanisms. In: Koletzko, B., Decsi, T., Molnár, D., de la Hunty, A. (eds) Early Nutrition Programming and Health Outcomes in Later Life. Advances in Experimental Medicine and Biology, vol 646. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9173-5_8
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