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Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome

Abstract

The concept of developmental origins of health and disease has been defined as the process through which the environment encountered before birth, or in infancy, shapes the long-term control of tissue physiology and homeostasis. The evidence for programming derives from a large number of experimental and epidemiological observations. Several nutritional interventions during diverse phases of pregnancy and lactation in rodents are associated with fetal and neonatal programming for metabolic syndrome. In this paper, recent experimental models and human epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related diseases are revisited.

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References

  1. Barker DJ . The fetal origins of adult hypertension. J Hypertens Suppl 1992; 10 (7): S39–S44.

    CAS  PubMed  Google Scholar 

  2. Lucas A . Programming by early nutrition in man. Ciba Found Symp 1991; 156: 38–50; discussion 50–35.

    CAS  PubMed  Google Scholar 

  3. Langley-Evans SC . Developmental programming of health and disease. Proc Nutr Soc 2006; 65 (1): 97–105.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Barraclough CA . Production of anovulatory, sterile rats by single injections of testosterone propionate. Endocrinology 1961; 68: 62–67.

    Article  CAS  PubMed  Google Scholar 

  5. Rose G . Familial patterns in ischaemic heart disease. Br J Prev Soc Med 1964; 18: 75–80.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Junien C, Nathanielsz P . Report on the IASO Stock Conference 2006: early and lifelong environmental epigenomic programming of metabolic syndrome, obesity and type II diabetes. Obes Rev 2007; 8 (6): 487–502.

    Article  CAS  PubMed  Google Scholar 

  7. Stanner SA, Bulmer K, Andres C, Lantseva OE, Borodina V, Poteen VV et al. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ 1997; 315 (7119): 1342–1348.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Ravelli GP, Stein ZA, Susser MW . Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 1976; 295 (7): 349–353.

    Article  CAS  PubMed  Google Scholar 

  9. Ravelli AC, van Der Meulen JH, Osmond C, Barker DJ, Bleker OP . Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999; 70 (5): 811–816.

    Article  CAS  PubMed  Google Scholar 

  10. Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP . Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Res 2001; 4 (5): 293–298.

    Article  CAS  PubMed  Google Scholar 

  11. Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJ . Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 1999; 318 (7181): 427–431.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Syddall HE, Sayer AA, Simmonds SJ, Osmond C, Cox V, Dennison EM et al. Birth weight, infant weight gain, and cause-specific mortality: the Hertfordshire Cohort Study. Am J Epidemiol 2005; 161 (11): 1074–1080.

    Article  CAS  PubMed  Google Scholar 

  13. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ . Weight in infancy and death from ischaemic heart disease. Lancet 1989; 2 (8663): 577–580.

    Article  CAS  PubMed  Google Scholar 

  14. Osmond C, Barker DJ, Winter PD, Fall CH, Simmonds SJ . Early growth and death from cardiovascular disease in women. BMJ 1993; 307 (6918): 1519–1524.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Martyn CN, Barker DJ, Osmond C . Mothers’ pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK. Lancet 1996; 348 (9037): 1264–1268.

    Article  CAS  PubMed  Google Scholar 

  16. Phillips DI, Jones A, Goulden PA . Birth weight, stress, and the metabolic syndrome in adult life. Ann NY Acad Sci 2006; 1083: 28–36.

    Article  CAS  PubMed  Google Scholar 

  17. Silveira VM, Horta BL . [Birth weight and metabolic syndrome in adults: meta-analysis]. Rev Saude Publica 2008; 42 (1): 10–18.

    Article  PubMed  Google Scholar 

  18. Salonen MK, Kajantie E, Osmond C, Forsen T, Yliharsila H, Paile-Hyvarinen M et al. Childhood growth and future risk of the metabolic syndrome in normal-weight men and women. Diabetes Metab 2009; 35 (2): 143–150.

    Article  CAS  PubMed  Google Scholar 

  19. Law CM, Shiell AW, Newsome CA, Syddall HE, Shinebourne EA, Fayers PM et al. Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation 2002; 105 (9): 1088–1092.

    Article  CAS  PubMed  Google Scholar 

  20. Hemachandra AH, Howards PP, Furth SL, Klebanoff MA . Birth weight, postnatal growth, and risk for high blood pressure at 7 years of age: results from the Collaborative Perinatal Project. Pediatrics 2007; 119 (6): e1264–e1270.

    Article  PubMed  Google Scholar 

  21. Singhal A, Cole TJ, Fewtrell M, Kennedy K, Stephenson T, Elias-Jones A et al. Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure? Circulation 2007; 115 (2): 213–220.

    Article  PubMed  Google Scholar 

  22. Barker DJ, Bagby SP, Hanson MA . Mechanisms of disease: in utero programming in the pathogenesis of hypertension. Nat Clin Pract Nephrol 2006; 2 (12): 700–707.

    Article  PubMed  Google Scholar 

  23. Hallan S, Euser AM, Irgens LM, Finken MJ, Holmen J, Dekker FW . Effect of intrauterine growth restriction on kidney function at young adult age: the Nord Trondelag Health (HUNT 2) Study. Am J Kidney Dis 2008; 51 (1): 10–20.

    Article  PubMed  Google Scholar 

  24. Simonetti GD, Raio L, Surbek D, Nelle M, Frey FJ, Mohaupt MG . Salt sensitivity of children with low birth weight. Hypertension 2008; 52 (4): 625–630.

    Article  CAS  PubMed  Google Scholar 

  25. Jones A, Beda A, Ward AM, Osmond C, Phillips DI, Moore VM et al. Size at birth and autonomic function during psychological stress. Hypertension 2007; 49 (3): 548–555.

    Article  CAS  PubMed  Google Scholar 

  26. Feldt K, Raikkonen K, Eriksson JG, Andersson S, Osmond C, Barker DJ et al. Cardiovascular reactivity to psychological stressors in late adulthood is predicted by gestational age at birth. J Hum Hypertens 2007; 21 (5): 401–410.

    Article  CAS  PubMed  Google Scholar 

  27. Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB . Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ 2000; 320 (7240): 967–971.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Ibanez L, Ong K, Dunger DB, de Zegher F . Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J Clin Endocrinol Metab 2006; 91 (6): 2153–2158.

    Article  CAS  PubMed  Google Scholar 

  29. Ibanez L, Suarez L, Lopez-Bermejo A, Diaz M, Valls C, de Zegher F . Early development of visceral fat excess after spontaneous catch-up growth in children with low birth weight. J Clin Endocrinol Metab 2008; 93 (3): 925–928.

    Article  CAS  PubMed  Google Scholar 

  30. Ibanez L, Lopez-Bermejo A, Suarez L, Marcos MV, Diaz M, de Zegher F . Visceral adiposity without overweight in children born small for gestational age. J Clin Endocrinol Metab 2008; 93 (6): 2079–2083.

    Article  CAS  PubMed  Google Scholar 

  31. Sayer AA, Syddall HE, Dennison EM, Gilbody HJ, Duggleby SL, Cooper C et al. Birth weight, weight at 1 y of age, and body composition in older men: findings from the Hertfordshire Cohort Study. Am J Clin Nutr 2004; 80 (1): 199–203.

    Article  CAS  PubMed  Google Scholar 

  32. Parsons TJ, Power C, Manor O . Fetal and early life growth and body mass index from birth to early adulthood in 1958 British cohort: longitudinal study. BMJ 2001; 323 (7325): 1331–1335.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Harder T, Rodekamp E, Schellong K, Dudenhausen JW, Plagemann A . Birth weight and subsequent risk of type 2 diabetes: a meta-analysis. Am J Epidemiol 2007; 165 (8): 849–857.

    Article  PubMed  Google Scholar 

  34. Whincup PH, Kaye SJ, Owen CG, Huxley R, Cook DG, Anazawa S et al. Birth weight and risk of type 2 diabetes: a systematic review. JAMA 2008; 300 (24): 2886–2897.

    Article  CAS  PubMed  Google Scholar 

  35. Phillips DI, Goulden P, Syddall HE, Aihie Sayer A, Dennison EM, Martin H et al. Fetal and infant growth and glucose tolerance in the Hertfordshire Cohort Study: a study of men and women born between 1931 and 1939. Diabetes 2005; 54 (Suppl 2): S145–S150.

    Article  CAS  PubMed  Google Scholar 

  36. Remacle C, Dumortier O, Bol V, Goosse K, Romanus P, Theys N et al. Intrauterine programming of the endocrine pancreas. Diabetes Obes Metab 2007; 9 (Suppl 2): 196–209.

    Article  CAS  PubMed  Google Scholar 

  37. Pulizzi N, Lyssenko V, Jonsson A, Osmond C, Laakso M, Kajantie E et al. Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes. Diabetologia 2009; 52 (5): 825–829.

    Article  CAS  PubMed  Google Scholar 

  38. Kajantie E, Barker DJ, Osmond C, Forsen T, Eriksson JG . Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort study. Int J Epidemiol 2008; 37 (2): 280–289.

    Article  PubMed  Google Scholar 

  39. Barker DJ, Osmond C, Forsen TJ, Kajantie E, Eriksson JG . Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005; 353 (17): 1802–1809.

    Article  CAS  PubMed  Google Scholar 

  40. Fall CH, Barker DJ, Osmond C, Winter PD, Clark PM, Hales CN . Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease. BMJ 1992; 304 (6830): 801–805.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Huxley R, Owen CG, Whincup PH, Cook DG, Colman S, Collins R . Birth weight and subsequent cholesterol levels: exploration of the ‘fetal origins’ hypothesis. JAMA 2004; 292 (22): 2755–2764.

    Article  CAS  PubMed  Google Scholar 

  42. Charney E, Goodman HC, McBride M, Lyon B, Pratt R . Childhood antecedents of adult obesity. Do chubby infants become obese adults? N Engl J Med 1976; 295 (1): 6–9.

    Article  CAS  PubMed  Google Scholar 

  43. Braddon FE, Rodgers B, Wadsworth ME, Davies JM . Onset of obesity in a 36 year birth cohort study. Br Med J (Clin Res Ed) 1986; 293 (6542): 299–303.

    Article  CAS  Google Scholar 

  44. Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S . Reasons for increasing trends in large for gestational age births. Obstet Gynecol 2004; 104 (4): 720–726.

    Article  PubMed  Google Scholar 

  45. Hediger ML, Overpeck MD, McGlynn A, Kuczmarski RJ, Maurer KR, Davis WW . Growth and fatness at three to six years of age of children born small- or large-for-gestational age. Pediatrics 1999; 104 (3): e33.

    Article  CAS  PubMed  Google Scholar 

  46. Dubois L, Girard M . Early determinants of overweight at 4.5 years in a population-based longitudinal study. Int J Obes (Lond) 2006; 30 (4): 610–617.

    Article  CAS  Google Scholar 

  47. Rasmussen F, Johansson M . The relation of weight, length and ponderal index at birth to body mass index and overweight among 18-year-old males in Sweden. Eur J Epidemiol 1998; 14 (4): 373–380.

    Article  CAS  PubMed  Google Scholar 

  48. Eriksson J, Forsen T, Tuomilehto J, Osmond C, Barker D . Size at birth, childhood growth and obesity in adult life. Int J Obes Relat Metab Disord 2001; 25 (5): 735–740.

    Article  CAS  PubMed  Google Scholar 

  49. Clarke WR, Lauer RM . Does childhood obesity track into adulthood? Crit Rev Food Sci Nutr 1993; 33 (4–5): 423–430.

    Article  CAS  PubMed  Google Scholar 

  50. Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, Stampfer MJ . Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 1996; 94 (12): 3246–3250.

    Article  CAS  PubMed  Google Scholar 

  51. Wei JN, Sung FC, Li CY, Chang CH, Lin RS, Lin CC et al. Low birth weight and high birth weight infants are both at an increased risk to have type 2 diabetes among schoolchildren in Taiwan. Diabetes Care 2003; 26 (2): 343–348.

    Article  PubMed  Google Scholar 

  52. Wang X, Liang L, Junfen FU, Lizhong DU . Metabolic syndrome in obese children born large for gestational age. Indian J Pediatr 2007; 74 (6): 561–565.

    Article  PubMed  Google Scholar 

  53. Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA . Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics 2003; 111 (3): e221–e226.

    Article  PubMed  Google Scholar 

  54. Boney CM, Verma A, Tucker R, Vohr BR . Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115 (3): e290–e296.

    Article  PubMed  Google Scholar 

  55. Giapros V, Evagelidou E, Challa A, Kiortsis D, Drougia A, Andronikou S . Serum adiponectin and leptin levels and insulin resistance in children born large for gestational age are affected by the degree of overweight. Clin Endocrinol (Oxf) 2007; 66 (3): 353–359.

    Article  CAS  Google Scholar 

  56. Vuguin PM . Animal models for small for gestational age and fetal programming of adult disease. Horm Res 2007; 68 (3): 113–123.

    CAS  PubMed  Google Scholar 

  57. Snoeck A, Remacle C, Reusens B, Hoet JJ . Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol Neonate 1990; 57 (2): 107–118.

    Article  CAS  PubMed  Google Scholar 

  58. Fernandez-Twinn DS, Ozanne SE, Ekizoglou S, Doherty C, James L, Gusterson B et al. The maternal endocrine environment in the low-protein model of intra-uterine growth restriction. Br J Nutr 2003; 90 (4): 815–822.

    Article  CAS  PubMed  Google Scholar 

  59. Langley SC, Jackson AA . Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci (Lond) 1994; 86 (2): 217–222; discussion 121.

    Article  CAS  Google Scholar 

  60. Nishina H, Green LR, McGarrigle HH, Noakes DE, Poston L, Hanson MA . Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep. J Physiol 2003; 553 (Pt 2): 637–647.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Ozanne SE . Metabolic programming in animals. Br Med Bull 2001; 60: 143–152.

    Article  CAS  PubMed  Google Scholar 

  62. Hales CN, Barker DJ . The thrifty phenotype hypothesis. Br Med Bull 2001; 60: 5–20.

    Article  CAS  PubMed  Google Scholar 

  63. Dahri S, Snoeck A, Reusens-Billen B, Remacle C, Hoet JJ . Islet function in offspring of mothers on low-protein diet during gestation. Diabetes 1991; 40 (Suppl 2): 115–120.

    Article  CAS  PubMed  Google Scholar 

  64. Petry CJ, Ozanne SE, Wang CL, Hales CN . Early protein restriction and obesity independently induce hypertension in 1-year-old rats. Clin Sci (Lond) 1997; 93 (2): 147–152.

    Article  CAS  Google Scholar 

  65. Shepherd PR, Crowther NJ, Desai M, Hales CN, Ozanne SE . Altered adipocyte properties in the offspring of protein malnourished rats. Br J Nutr 1997; 78 (1): 121–129.

    Article  CAS  PubMed  Google Scholar 

  66. Reusens B, Remacle C . Programming of the endocrine pancreas by the early nutritional environment. Int J Biochem Cell Biol 2006; 38 (5–6): 913–922.

    Article  CAS  PubMed  Google Scholar 

  67. Petrik J, Reusens B, Arany E, Remacle C, Coelho C, Hoet JJ et al. A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology 1999; 140 (10): 4861–4873.

    Article  CAS  PubMed  Google Scholar 

  68. Boujendar S, Reusens B, Merezak S, Ahn MT, Arany E, Hill D et al. Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets. Diabetologia 2002; 45 (6): 856–866.

    Article  CAS  PubMed  Google Scholar 

  69. Dahri S, Reusens B, Remacle C, Hoet JJ . Nutritional influences on pancreatic development and potential links with non-insulin-dependent diabetes. Proc Nutr Soc 1995; 54 (2): 345–356.

    Article  CAS  PubMed  Google Scholar 

  70. Cherif H, Reusens B, Dahri S, Remacle C . A protein-restricted diet during pregnancy alters in vitro insulin secretion from islets of fetal Wistar rats. J Nutr 2001; 131 (5): 1555–1559.

    Article  CAS  PubMed  Google Scholar 

  71. Sparre T, Reusens B, Cherif H, Larsen MR, Roepstorff P, Fey SJ et al. Intrauterine programming of fetal islet gene expression in rats—effects of maternal protein restriction during gestation revealed by proteome analysis. Diabetologia 2003; 46 (11): 1497–1511.

    Article  CAS  PubMed  Google Scholar 

  72. Park KS, Kim SK, Kim MS, Cho EY, Lee JH, Lee KU et al. Fetal and early postnatal protein malnutrition cause long-term changes in rat liver and muscle mitochondria. J Nutr 2003; 133 (10): 3085–3090.

    Article  CAS  PubMed  Google Scholar 

  73. Lee HK, Song JH, Shin CS, Park DJ, Park KS, Lee KU et al. Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1998; 42 (3): 161–167.

    Article  CAS  PubMed  Google Scholar 

  74. Lee HK . Evidence that the mitochondrial genome is the thrifty genome. Diabetes Res Clin Pract 1999; 45 (2–3): 127–135.

    Article  CAS  PubMed  Google Scholar 

  75. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM . Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36 (1): 62–67.

    Article  CAS  PubMed  Google Scholar 

  76. Gluckman PD, Hanson MA . The developmental origins of the metabolic syndrome. Trends Endocrinol Metab 2004; 15 (4): 183–187.

    Article  CAS  PubMed  Google Scholar 

  77. Desai M, Hales CN . Role of fetal and infant growth in programming metabolism in later life. Biol Rev Camb Philos Soc 1997; 72 (2): 329–348.

    Article  CAS  PubMed  Google Scholar 

  78. Lucas A, Baker BA, Desai M, Hales CN . Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring. Br J Nutr 1996; 76 (4): 605–612.

    Article  CAS  PubMed  Google Scholar 

  79. Barker DJ, Martyn CN, Osmond C, Hales CN, Fall CH . Growth in utero and serum cholesterol concentrations in adult life. BMJ 1993; 307 (6918): 1524–1527.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Desai M, Gayle D, Babu J, Ross MG . Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition. Am J Physiol Regul Integr Comp Physiol 2005; 288 (1): R91–R96.

    Article  CAS  PubMed  Google Scholar 

  81. Gregorio BM, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB . Maternal fish oil supplementation benefits programmed offspring from rat dams fed low-protein diet. Am J Obstet Gynecol 2008; 199 (1): 82 e81–82 e87.

    Article  CAS  Google Scholar 

  82. Desai M, Byrne CD, Zhang J, Petry CJ, Lucas A, Hales CN . Programming of hepatic insulin-sensitive enzymes in offspring of rat dams fed a protein-restricted diet. Am J Physiol 1997; 272 (5 Pt 1): G1083–G1090.

    CAS  PubMed  Google Scholar 

  83. Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB . Hepatic structural alteration in adult programmed offspring (severe maternal protein restriction) is aggravated by post-weaning high-fat diet. Br J Nutr 2007; 98 (6): 1159–1169.

    Article  CAS  PubMed  Google Scholar 

  84. Bellinger L, Langley-Evans SC . Fetal programming of appetite by exposure to a maternal low-protein diet in the rat. Clin Sci (Lond) 2005; 109 (4): 413–420.

    Article  CAS  Google Scholar 

  85. Langley-Evans SC, Bellinger L, McMullen S . Animal models of programming: early life influences on appetite and feeding behaviour. Matern Child Nutr 2005; 1 (3): 142–148.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD . Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 2000; 279 (1): E83–E87.

    Article  CAS  PubMed  Google Scholar 

  87. Amiel SA, Caprio S, Sherwin RS, Plewe G, Haymond MW, Tamborlane WV . Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J Clin Endocrinol Metab 1991; 72 (2): 277–282.

    Article  CAS  PubMed  Google Scholar 

  88. Steinberg HO, Baron AD . Vascular function, insulin resistance and fatty acids. Diabetologia 2002; 45 (5): 623–634.

    Article  CAS  PubMed  Google Scholar 

  89. Rahmouni K, Morgan DA, Morgan GM, Mark AL, Haynes WG . Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes 2005; 54 (7): 2012–2018.

    Article  CAS  PubMed  Google Scholar 

  90. Almeida JR, Mandarim-de-Lacerda CA . Maternal gestational protein-calorie restriction decreases the number of glomeruli and causes glomerular hypertrophy in adult hypertensive rats. Am J Obstet Gynecol 2005; 192 (3): 945–951.

    Article  PubMed  Google Scholar 

  91. Catta-Preta M, Oliveira DA, Mandarim-de-Lacerda CA, Aguila MB . Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of low-protein pregnancies. Life Sci 2006; 80 (3): 219–229.

    Article  CAS  PubMed  Google Scholar 

  92. Douglas-Denton RN, McNamara BJ, Hoy WE, Hughson MD, Bertram JF . Does nephron number matter in the development of kidney disease? Ethn Dis 2006; 16 (2 Suppl 2): S2-40–S2-45.

    Google Scholar 

  93. Pires KMP, Aguila MB, Mandarim-de-Lacerda CA . Early renal structure alteration in rat offspring from dams fed low protein diet. Life Sci 2006; 79 (22): 2128–2134.

    Article  CAS  PubMed  Google Scholar 

  94. Villar-Martini VC, Carvalho JJ, Neves MF, Aguila MB, Mandarim-de-Lacerda CA . Hypertension and kidney alterations in rat offspring from low protein pregnancies. J Hypertens 2009; 27 (Suppl 6): S47–S51.

    Article  CAS  Google Scholar 

  95. Kriz W, Gretz N, Lemley KV . Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 1998; 54 (3): 687–697.

    Article  CAS  PubMed  Google Scholar 

  96. Woods LL, Ingelfinger JR, Rasch R . Modest maternal protein restriction fails to program adult hypertension in female rats. Am J Physiol Regul Integr Comp Physiol 2005; 289 (4): R1131–R1136.

    Article  CAS  PubMed  Google Scholar 

  97. Pinheiro AR, Salvucci ID, Aguila MB, Mandarim-de-Lacerda CA . Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats. Clin Sci (Lond) 2008; 114 (5): 381–392.

    Article  CAS  Google Scholar 

  98. Zambrano E, Martínez-Samayoa PM, Bautista CJ, Deas M, Guillen L, Rodriguez-Gonzalez GL et al. Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 2005; 566 (Pt 1): 225–236.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Kingdom JC, Hayes M, McQueen J, Howatson AG, Lindop GB . Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney. Kidney Int 1999; 55 (2): 424–429.

    Article  CAS  PubMed  Google Scholar 

  100. Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ . Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med 2000; 160 (10): 1472–1476.

    Article  CAS  PubMed  Google Scholar 

  101. Barker DJ . The intrauterine origins of cardiovascular disease. Acta Paediatr Suppl 1993; 82 (Suppl 391): 93–99; discussion 100.

    Article  PubMed  Google Scholar 

  102. Vickers MH, Breier BH, McCarthy D, Gluckman PD . Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Am J Physiol Regul Integr Comp Physiol 2003; 285 (1): R271–R273.

    Article  CAS  PubMed  Google Scholar 

  103. Armitage JA, Taylor PD, Poston L . Experimental models of developmental programming: consequences of exposure to an energy rich diet during development. J Physiol 2005; 565 (Pt 1): 3–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  104. Taylor PD, Poston L . Developmental programming of obesity in mammals. Exp Physiol 2007; 92 (2): 287–298.

    Article  CAS  PubMed  Google Scholar 

  105. Symonds ME, Sebert SP, Hyatt MA, Budge H . Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol 2009; 5 (11): 604–610.

    Article  CAS  PubMed  Google Scholar 

  106. Patel MS, Srinivasan M . Metabolic programming due to alterations in nutrition in the immediate postnatal period. J Nutr 2010; 140 (3): 658–661.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Patel MS, Srinivasan M . Metabolic programming due to alterations in nutrition in the immediate postnatal period. J Nutr 2010; 140 (3): 658–661.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  108. Plagemann A, Harder T, Rake A, Voits M, Fink H, Rohde W et al. Perinatal elevation of hypothalamic insulin, acquired malformation of hypothalamic galaninergic neurons, and syndrome x-like alterations in adulthood of neonatally overfed rats. Brain Res 1999; 836 (1–2): 146–155.

    Article  CAS  PubMed  Google Scholar 

  109. Holemans K, Caluwaerts S, Poston L, Van Assche FA . Diet-induced obesity in the rat: a model for gestational diabetes mellitus. Am J Obstet Gynecol 2004; 190 (3): 858–865.

    Article  PubMed  Google Scholar 

  110. Napoli C, de Nigris F, Welch JS, Calara FB, Stuart RO, Glass CK et al. Maternal hypercholesterolemia during pregnancy promotes early atherogenesis in LDL receptor-deficient mice and alters aortic gene expression determined by microarray. Circulation 2002; 105 (11): 1360–1367.

    Article  CAS  PubMed  Google Scholar 

  111. Zhang J, Wang C, Terroni PL, Cagampang FR, Hanson M, Byrne CD . High-unsaturated-fat, high-protein, and low-carbohydrate diet during pregnancy and lactation modulates hepatic lipid metabolism in female adult offspring. Am J Physiol Regul Integr Comp Physiol 2005; 288 (1): R112–R118.

    Article  CAS  PubMed  Google Scholar 

  112. Bayol SA, Farrington SJ, Stickland NC . A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring. Br J Nutr 2007; 98 (4): 843–851.

    Article  CAS  PubMed  Google Scholar 

  113. Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EH et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 2008; 51 (2): 383–392.

    Article  CAS  PubMed  Google Scholar 

  114. Plagemann A . Perinatal programming and functional teratogenesis: impact on body weight regulation and obesity. Physiol Behav 2005; 86 (5): 661–668.

    Article  CAS  PubMed  Google Scholar 

  115. Tessari P, Coracina A, Cosma A, Tiengo A . Hepatic lipid metabolism and non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2009; 19 (4): 291–302.

    Article  CAS  PubMed  Google Scholar 

  116. Desai M, Gayle D, Han G, Ross MG . Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth-restricted offspring. Reprod Sci 2007; 14 (4): 329–337.

    Article  PubMed  Google Scholar 

  117. Taylor PD, McConnell J, Khan IY, Holemans K, Lawrence KM, Asare-Anane H et al. Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol 2005; 288 (1): R134–R139.

    Article  CAS  PubMed  Google Scholar 

  118. Buckley AJ, Keseru B, Briody J, Thompson M, Ozanne SE, Thompson CH . Altered body composition and metabolism in the male offspring of high fat-fed rats. Metabolism 2005; 54 (4): 500–507.

    Article  CAS  PubMed  Google Scholar 

  119. Gregorio BM, Souza-Mello V, Carvalho JJ, Mandarim-de-Lacerda CA, Aguila MB . Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring. Am J Obstet Gynecol 2010; 203 (5): 495 e491–495 e498.

    Article  CAS  Google Scholar 

  120. den Boer M, Voshol PJ, Kuipers F, Havekes LM, Romijn JA . Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arterioscler Thromb Vasc Biol 2004; 24 (4): 644–649.

    Article  CAS  PubMed  Google Scholar 

  121. Siemelink M, Verhoef A, Dormans JA, Span PN, Piersma AH . Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring. Diabetologia 2002; 45 (10): 1397–1403.

    Article  CAS  PubMed  Google Scholar 

  122. Korotkova M, Gabrielsson BG, Holmang A, Larsson BM, Hanson LA, Strandvik B . Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids. Am J Physiol Regul Integr Comp Physiol 2005; 288 (3): R575–R579.

    Article  CAS  PubMed  Google Scholar 

  123. Khan IY, Taylor PD, Dekou V, Seed PT, Lakasing L, Graham D et al. Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 2003; 41 (1): 168–175.

    Article  CAS  PubMed  Google Scholar 

  124. Khan I, Dekou V, Hanson M, Poston L, Taylor P . Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring. Circulation 2004; 110 (9): 1097–1102.

    Article  CAS  PubMed  Google Scholar 

  125. Tamaya-Mori N, Uemura K, Iguchi A . Gender differences in the dietary lard-induced increase in blood pressure in rats. Hypertension 2002; 39 (5): 1015–1020.

    Article  CAS  PubMed  Google Scholar 

  126. Parente LB, Aguila MB, Mandarim-de-Lacerda CA . Deleterious effects of high-fat diet on perinatal and postweaning periods in adult rat offspring. Clin Nutr 2008; 27 (4): 623–634.

    Article  CAS  PubMed  Google Scholar 

  127. Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L . Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol 2004; 561 (Pt 2): 355–377.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Weisinger HS, Armitage JA, Sinclair AJ, Vingrys AJ, Burns PL, Weisinger RS . Perinatal omega-3 fatty acid deficiency affects blood pressure later in life. Nat Med 2001; 7 (3): 258–259.

    Article  CAS  PubMed  Google Scholar 

  129. Weinstock M, Matlina E, Maor GI, Rosen H, McEwen BS . Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat. Brain Res 1992; 595 (2): 195–200.

    Article  CAS  PubMed  Google Scholar 

  130. Liu L, Li A, Matthews SG . Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects. Am J Physiol Endocrinol Metab 2001; 280 (5): E729–E739.

    Article  CAS  PubMed  Google Scholar 

  131. Pratt JH . Low-renin hypertension: more common than we think? Cardiol Rev 2000; 8 (4): 202–206.

    Article  CAS  PubMed  Google Scholar 

  132. Haddy FJ, Pamnani MB . Role of ouabain-like factors and Na-K-ATPase inhibitors in hypertension—some old and recent findings. Clin Exp Hypertens 1998; 20 (5–6): 499–508.

    Article  CAS  PubMed  Google Scholar 

  133. Jaitovich A, Bertorello AM . Salt, Na+,K+-ATPase and hypertension. Life Sci 2010; 86 (3–4): 73–78.

    Article  CAS  PubMed  Google Scholar 

  134. Iwamoto T, Kita S . Hypertension, Na+/Ca2+ exchanger, and Na+, K+-ATPase. Kidney Int 2006; 69 (12): 2148–2154.

    Article  CAS  PubMed  Google Scholar 

  135. Jaitovich A, Bertorello AM . Salt, Na(+),K(+)-ATPase and hypertension. Life Sci 2010; 86 (3–4): 73–78.

    Article  CAS  PubMed  Google Scholar 

  136. Turner N, Else PL, Hulbert AJ . Docosahexaenoic acid (DHA) content of membranes determines molecular activity of the sodium pump: implications for disease states and metabolism. Naturwissenschaften 2003; 90 (11): 521–523.

    Article  CAS  PubMed  Google Scholar 

  137. Wu BJ, Else PL, Storlien LH, Hulbert AJ . Molecular activity of Na(+)/K(+)-ATPase from different sources is related to the packing of membrane lipids. J Exp Biol 2001; 204 (Pt 24): 4271–4280.

    Article  CAS  PubMed  Google Scholar 

  138. Kirk SL, Samuelsson AM, Argenton M, Dhonye H, Kalamatianos T, Poston L et al. Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring. PLoS One 2009; 4 (6): e5870.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  139. Franke K, Harder T, Aerts L, Melchior K, Fahrenkrog S, Rodekamp E et al. ‘Programming’ of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats. Brain Res 2005; 1031 (2): 276–283.

    Article  CAS  PubMed  Google Scholar 

  140. Bouret SG . Early life origins of obesity: role of hypothalamic programming. J Pediatr Gastroenterol Nutr 2009; 48 (Suppl 1): S31–S38.

    Article  PubMed  Google Scholar 

  141. 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 (1): 37–44.

    Article  CAS  PubMed  Google Scholar 

  142. Levin BE, Dunn-Meynell AA, Banks WA . Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset. Am J Physiol Regul Integr Comp Physiol 2004; 286 (1): R143–R150.

    Article  CAS  PubMed  Google Scholar 

  143. Ferezou-Viala J, Roy AF, Serougne C, Gripois D, Parquet M, Bailleux V et al. Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring. Am J Physiol Regul Integr Comp Physiol 2007; 293 (3): R1056–R1062.

    Article  CAS  PubMed  Google Scholar 

  144. Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA . Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr 2007; 97 (6): 1036–1046.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  145. Delage B, Dashwood RH . Dietary manipulation of histone structure and function. Annu Rev Nutr 2008; 28: 347–366.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  146. Bird A . DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16 (1): 6–21.

    Article  CAS  PubMed  Google Scholar 

  147. Plagemann A, Harder T, Brunn M, Harder A, Roepke K, Wittrock-Staar M et al. Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome. J Physiol 2009; 587 (Pt 20): 4963–4976.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  148. Drake AJ, Tang JI, Nyirenda MJ . Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease. Clin Sci (Lond) 2007; 113 (5): 219–232.

    Article  CAS  Google Scholar 

  149. Goldberg AD, Allis CD, Bernstein E . Epigenetics: a landscape takes shape. Cell 2007; 128 (4): 635–638.

    Article  CAS  PubMed  Google Scholar 

  150. Amaral PP, Mattick JS . Noncoding RNA in development. Mamm Genome 2008; 19 (7–8): 454–492.

    Article  CAS  PubMed  Google Scholar 

  151. Gluckman PD, Hanson MA, Buklijas T, Low FM, Beedle AS . Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol 2009; 5 (7): 401–408.

    Article  CAS  PubMed  Google Scholar 

  152. Langley-Evans SC . Nutritional programming of disease: unravelling the mechanism. J Anat 2009; 215 (1): 36–51.

    Article  PubMed  Google Scholar 

  153. Waterland RA, Jirtle RL . Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 2003; 23 (15): 5293–5300.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  154. Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC . Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr 2007; 97 (6): 1064–1073.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  155. Aagaard-Tillery KM, Grove K, Bishop J, Ke X, Fu Q, McKnight R et al. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol 2008; 41 (2): 91–102.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  156. Vucetic Z, Kimmel J, Totoki K, Hollenbeck E, Reyes TM . Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology 2010; 151 (10): 4756–4764.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  157. Waterland RA . Epigenetic epidemiology of obesity: application of epigenomic technology. Nutr Rev 2008; 66 (Suppl 1): S21–S23.

    Article  PubMed  Google Scholar 

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de Gusmão Correia, M., Volpato, A., Águila, M. et al. Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome. J Hum Hypertens 26, 405–419 (2012). https://doi.org/10.1038/jhh.2011.61

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  • DOI: https://doi.org/10.1038/jhh.2011.61

Keywords

  • fetal programming
  • developmental origins of disease
  • metabolic syndrome
  • obesity

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