Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Programming of obesity and cardiovascular disease

International Journal of Obesity volume 28, pages S46–S53 (2004)Cite this article

Abstract

BACKGROUND: There is evidence that malnutrition in early life induces a growth retardation leading, in adult life, to manifest components of the metabolic syndrome. However, the impact on obesity seems less clearly established.

OBJECTIVE: To review the effects of foetal and postnatal malnutrition on the programming of obesity in the context of the metabolic syndrome, as well as the link between central obesity and cardiovascular diseases.

METHODS: Included in the review were recent papers exploring the mechanisms linking maternal nutrition with impaired foetal growth and later obesity, cardiovascular disease, hypertension and diabetes in humans and animals.

RESULTS: The programming of obesity during foetal and early postnatal life depends of the timing of maternal malnutrition as well as the postnatal environment. Obesity arises principally in offspring submitted to malnutrition during early stages of gestation and which presented early catch-up growth. The programming may involve the dysregulation of appetite control or the hormonal environment leading to a context favourable to obesity development (hypersecretion of corticosteroids, hyperinsulinaemia and hyperleptinaemia and anomalies in the IGF axis). Adipose tissue secretes actively several factors implicated in inflammation, blood pressure, coagulation and fibrinolysis. The programmed development of intra-abdominal obesity after early growth restriction may thus favour higher prevalence of hypertension and cardiovascular diseases.

CONCLUSIONS: Abdominal obesity appears in malnourished offspring and is aggravated by early catch-up growth. Higher rates of intra-abdominal obesity observed after growth restriction may participate to hypertension and create atherothrombotic conditions leading to the development of cardiovascular diseases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Mercer JG, O'Reilly LM, Morgan PJ . Increasing the impact of European obesity research in preparation for the European research area: a report on the 2003 European Commission Obesity Workshop. Obes Rev 2004; 5: 79–85.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Hales CN, Barker DJ, Clarck PM, Cox LJ, Fall C, Osmond C, Winter PD . Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991; 303: 1019–1022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Hales CN, Barker DJ . Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992; 35: 595–601.

    Article  CAS  PubMed  Google Scholar 

  6. Ong KK, Dunger DB . Perinatal growth failure: the road to obesity, insulin resistance and cardiovascular diseases in adults. Best Pract Res Clin Endocrinol Metab 2002; 16: 191–207.

    Article  CAS  PubMed  Google Scholar 

  7. Holemans K, Aerts L, Van Assche FA . Fetal growth restriction and consequences for the offspring in animal models. J Soc Gynecol Invest 2003; 10: 392–399.

    Article  CAS  Google Scholar 

  8. Bertram CE, Hanson MA . Animal models and programming of the metabolic syndrome. Br Med Bull 2001; 60: 103–121.

    Article  CAS  PubMed  Google Scholar 

  9. Reusens B, Remacle C . Intergenerational effect of an adverse intrauterine environnement on perturbation of glucose metabolism. Twin Res 2001; 4: 406–411.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Langley-Evans SC . Critical differences between two low protein diet protocols in the programming of hypertension in the rat. Int J Food Sci Nutr 2000; 51: 11–17.

    Article  CAS  PubMed  Google Scholar 

  12. Hales CN, Desai M, Ozanne SE, Crowther NJ . Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis. Biochem Soc Trans 1996; 24: 341–350.

    Article  CAS  PubMed  Google Scholar 

  13. Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP . Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 2000; 127: 4195–4202.

    CAS  PubMed  Google Scholar 

  14. Boujendar S, Reusens B, Merezak S, Ahn MT, Arany E, Hill D, Remacle C . 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: 856–866.

    Article  CAS  PubMed  Google Scholar 

  15. Cherif H, Reusens B, Ahn MT, Hoet JJ, Remacle C . Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet. J Endocrinol 1998; 159: 341–348.

    Article  CAS  PubMed  Google Scholar 

  16. 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: 345–356.

    Article  CAS  PubMed  Google Scholar 

  17. Ozanne SE, Hales CN . Early programming of glucose–insulin metabolism. Trends Endocrinol Metab 2002; 13: 368–373.

    Article  CAS  PubMed  Google Scholar 

  18. Garofano A, Czernichow P, Breant B . Effect of ageing on beta-cell mass and function in rats malnourished during the perinatal period. Diabetologia 1999; 42: 711–718.

    Article  CAS  PubMed  Google Scholar 

  19. Vickers MH, Ikenasio BA, Breier BH . IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming. Endocrinology 2001; 142: 3964–3973.

    Article  CAS  PubMed  Google Scholar 

  20. Vickers MH, Reddy S, Ikenasio BA, Breier BH . Dysregulation of the adipoinsular axis: a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming. J Endocrinol 2001; 170: 323–332.

    Article  CAS  PubMed  Google Scholar 

  21. Simmons RA, Templeton LJ, Gertz SJ . Intrauterine growth retardation lead to the development of type 2 diabetes in the rat. Diabetes 2001; 50: 2279–2286.

    Article  CAS  PubMed  Google Scholar 

  22. Jansson T, Lambert GW . Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3–4 months of age. J Hypertens 1999; 17: 1239–1248.

    Article  CAS  PubMed  Google Scholar 

  23. Oken E, Gillman MW . Fetal origins of obesity. Obes Res 2003; 11: 496–506.

    Article  PubMed  Google Scholar 

  24. Rogers I . The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life. Int J Obes Relat Metab Disord 2003; 27: 755–777.

    Article  PubMed  Google Scholar 

  25. Eriksson J, Forsen T, Osmond C, Barker D . Obesity from cradle to grave. Int J Obes Relat Metab Disord 2003; 27: 722–727.

    Article  CAS  PubMed  Google Scholar 

  26. Dabelea D, Pettitt DJ . Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility. J Pediatr Endocrinol Metab 2001; 14: 1085–1091.

    Article  CAS  PubMed  Google Scholar 

  27. Toschke AM, Koletzko B, Slikker Jr W, Hermann M, von Kries R . Childhood obesity is associated with maternal smoking in pregnancy. Eur J Pediatr 2002; 161: 445–448.

    Article  CAS  PubMed  Google Scholar 

  28. Power C, Jefferis BJ . Fetal environment and subsequent obesity: a study of maternal smoking. Int J Epidemiol 2002; 31: 413–419.

    Article  PubMed  Google Scholar 

  29. Prentice AM . Obesity and its potential mechanistic basis. Br Med Bull 2001; 60: 51–67.

    Article  CAS  PubMed  Google Scholar 

  30. Roseboom TJ, van der Meulen JHO, Ravelli ACJ, Osmond C, Barker DJP, Bleker OP . Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 2001; 185: 93–98.

    Article  CAS  PubMed  Google Scholar 

  31. Ravelli ACJ, van der Meulen JHP, Osmond C, Barker DJP, Bleker O . Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999; 70: 811–816.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Stanner SA, Yudkin JS . Fetal programming and the Leningrad Siege study. Twin Res 2001; 4: 287–292.

    Article  CAS  PubMed  Google Scholar 

  34. Walker SP, Gaskin PS, Powell CA, Bennett FI . The effects of birth weight and postnatal linear growth retardation on body mass index, fatness and fat distribution in mid and late childhood. Public Health Nutr 2002; 5: 391–396.

    Article  PubMed  Google Scholar 

  35. Yajnik CS . Early life origins of insulin resistance and type 2 diabetes in India and other asian countries. J Nutr 2004; 134: 205–210.

    Article  CAS  PubMed  Google Scholar 

  36. Singhal A, Wells J, Cole TJ, Fewtrell M, Lucas A . Programming of lean body mass: a link between birth weight, obesity, and cardiovascular disease? Am J Clin Nutr 2003; 77: 726–730.

    Article  CAS  PubMed  Google Scholar 

  37. Ailhaud G, Guesnet P . Fatty acid composition of fats is an early determinant of childhood obesity: a short review and an opinion. Obes Rev 2004; 5: 21–26.

    Article  CAS  PubMed  Google Scholar 

  38. Petry CJ, Ozanne SE, Hales CN . Programming of intermediary metabolism. Mol Cell Endocrinol 2001; 185: 81–91.

    Article  CAS  PubMed  Google Scholar 

  39. Holness MJ, Sugden MC . Antecedent protein restriction exacerbates development of impaired insulin action after high-fat feeding. Am J Physiol 1999; 276: E85–E93.

    CAS  PubMed  Google Scholar 

  40. Stocker C, O'Dowd J, Morton NM, Wargent E, Sennitt MV, Hislop D, Glund S, Seckl JR, Arch JR, Cawthorne MA . Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation. Int J Obes Relat Metab Disord 2004; 28: 129–136.

    Article  CAS  PubMed  Google Scholar 

  41. Ozanne SE, Lewis R, Jennings BJ, Hales CN . Early programming of weight gain in mice prevents the induction of obesity by a highly palatable diet. Clin Sci 2004; 106: 141–145.

    Article  CAS  Google Scholar 

  42. Breier BH, Vickers MH, Ikenasio BA, Chan KY, Wong WP . Fetal programming of appetite and obesity. Mol Cell Endocrinol 2001; 185: 73–79.

    Article  CAS  PubMed  Google Scholar 

  43. Anguita RM, Sigulem DM, Sawaya AL . Intrauterine food restriction is associated with obesity in young rats. J Nutr 1993; 123: 1421–1428.

    CAS  PubMed  Google Scholar 

  44. Jones AP, Pothos EN, Rada P, Olster DH, Hoebel BG . Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring. Brain Res Dev Brain Res 1995; 88: 127–131.

    Article  CAS  PubMed  Google Scholar 

  45. Bispham J, Gopalakrishnan GS, Dandrea J, Wilson V, Budge H, Keisler DH, Broughton Pipkin F, Stephenson T, Symonds ME . Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development. Endocrinology 2003; 144: 3575–3585.

    Article  CAS  PubMed  Google Scholar 

  46. Gopalakrishnan GS, Gardner DS, Rhind SM, Rae MT, Kyle CE, Brooks AN, Walker RM, Ramsay MM, Keisler DH, Stephenson T, Symonds ME . Programming of adult cardiovascular function after early maternal undernutrition in sheep. Am J Physiol Regul Integr Comp Physiol 2004; 287: R12–R20.

    Article  CAS  PubMed  Google Scholar 

  47. Massiera F, Saint-Marc P, Seydoux J, Murata T, Kobayashi T, Narumiya S, Guesnet P, Amri EZ, Negrel R, Ailhaud G . Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res 2003; 44: 271–279.

    Article  CAS  PubMed  Google Scholar 

  48. Ong KK, Ahmed ML, Dunger DB . The role of leptin in human growth and puberty. Acta Paediatr 1999; 88 (Suppl): 95–98.

    Article  CAS  Google Scholar 

  49. Bjorntorp P, Rosmond R . Obesity and cortisol. Nutrition 2000; 16: 924–936.

    Article  CAS  PubMed  Google Scholar 

  50. Ward AM, Syddall HE, Wood PJ, Chrousos GP, Phillips DI . Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis: low birth weight and central HPA regulation. J Clin Endocrinol Metab 2004; 89: 1227–1233.

    Article  CAS  PubMed  Google Scholar 

  51. Lesage J, Blondeau B, Grino M, Breant B, Dupouy JP . Maternal undernutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamo-pituitary adrenal axis in the newborn rat. Endocrinology 2001; 142: 1692–1702.

    Article  CAS  PubMed  Google Scholar 

  52. Langley-Evans SC, Nwagwu M . Impaired growth and increased glucocorticoid-sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets. Life Sci 1998; 63: 605–615.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  54. Matthews SG, Phillips DIW, Challis JRG, Cox DB, Thomas EJ, McMillen C, Lye SJ, McDonald RB, Wintour EM, Morrison JL, Sloboda DM . The hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes in early life: problems and perspectives. In: Barker DJP (ed) Fetal Origin of Cardiovascular and Lung Disease. Marcel Dekker Inc.: New York; 2001. pp 229–240.

    Google Scholar 

  55. Woodall SM, Breier BH, Johnston BM, Gluckman PD . A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: effects on the somatotrophic axis and postnatal growth. J Endocrinol 1996; 150: 231–242.

    Article  CAS  PubMed  Google Scholar 

  56. Olausson H, Sohlstrom A . Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tissues from guinea pigs. J Endocrinol 2003; 179: 437–445.

    Article  CAS  PubMed  Google Scholar 

  57. Muaku SM, Beauloye V, Thissen JP, Underwood LE, Ketelslegers JM, Maiter D . Effects of maternal protein malnutrition on fetal growth, plasma insulin-like growth factors, insulin-like growth factor binding proteins, and liver insulin-like growth factor gene expression in the rat. Pediatr Res 1995; 37: 334–342.

    Article  CAS  PubMed  Google Scholar 

  58. El-Khattabi I, Gregoire F, Remacle C, Reusens B . Isocaloric maternal low-protein diet alters IGF-I, IGFBPs, and hepatocyte proliferation in the fetal rat. Am J Physiol Endocrinol Metab 2003; 285: E991–E1000.

    Article  CAS  PubMed  Google Scholar 

  59. Bieswal F, Hay SM, Mckinnon C, Reusens B, Cuignet M, Rees WD, Remacle C . Prenatal protein restriction does not affect the proliferation and differentiation of rat preadipocytes. J Nutr 2004; 134: 1493–1499.

    Article  CAS  PubMed  Google Scholar 

  60. MacDougald OA, Mandrup S . Adipogenesis: forces that tip the scales. Trends Endocrinol Metab 2002; 13: 5–11.

    Article  CAS  PubMed  Google Scholar 

  61. Spiegelman BM, Flier JS . Obesity and the regulation of energy balance. Cell 2001; 104: 531–543.

    Article  CAS  PubMed  Google Scholar 

  62. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT . The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709–2716.

    Article  PubMed  Google Scholar 

  63. Sowers JR . Obesity as a cardiovascular risk factor. Am J Med 2003; 115 (Suppl 8A): 37S–41S.

    Article  CAS  PubMed  Google Scholar 

  64. Rajala MW, Scherer PE . Minireview: The adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003; 144: 3765–3773.

    Article  CAS  PubMed  Google Scholar 

  65. Gregoire FM . Adipocyte differentiation: from fibroblast to endocrine cell. Exp Biol Med 2001; 226: 997–1002.

    Article  CAS  Google Scholar 

  66. Banerjee RR, Lazar MA . Resistin: molecular history and prognosis. J Mol Med 2003; 81: 218–226.

    Article  CAS  PubMed  Google Scholar 

  67. Sartipy P, Loskutoff DJ . Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 2003; 100: 7265–7270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, Kishida K, Komuro R, Ouchi N, Kihara S, Nagai R, Funahashi T, Matsuzawa Y . Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 2002; 277: 37487–37491.

    Article  CAS  PubMed  Google Scholar 

  69. Goto D, Fujii S, Kaneko T, Furumoto T, Sugawara T, Tarikuz Zaman AK, Imagawa S, Dong J, Nakai Y, Mishima T, Sobel BE, Kitabatake A . Intracellular signal transduction modulating expression of plasminogen activator inhibitor-1 in adipocytes. Biochem Pharmacol 2003; 65: 1907–1914.

    Article  CAS  PubMed  Google Scholar 

  70. Yamamoto K, Shimakawa T, Yi H, Isobe K, Kojima T, Loskutoff DJ, Saito H . Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse. Blood 2002; 100: 4011–4018.

    Article  CAS  PubMed  Google Scholar 

  71. Huxley RR, Shiell AW, Law CM . The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 2000; 18: 815–831.

    Article  CAS  PubMed  Google Scholar 

  72. Clarke KJ, Zhong Q, Schwartz DD, Coleman ES, Kemppainen RJ, Judd RL . Regulation of adiponectin secretion by endothelin-1. Biochem Biophys Res Commun 2003; 312: 945–949.

    Article  CAS  PubMed  Google Scholar 

  73. Serazin V, Dieudonne MN, Morot M, de Mazancourt P, Giudicelli Y . cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue. Am J Physiol Endocrinol Metab 2004; 286: E434–E438.

    Article  CAS  PubMed  Google Scholar 

  74. Aneja A, El-Atat F, McFarlane SI, Sowers JR . Hypertension and obesity. Recent Prog Horm Res 2004; 59: 169–205.

    Article  CAS  PubMed  Google Scholar 

  75. McMullen S, Gardner DS, Langley-Evans SC . Prenatal programming of angiotensin II type 2 receptor expression in the rat. Br J Nutr 2004; 91: 133–140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dodic M, Moritz K, Koukoulas I, Wintour EM . Programmed hypertension: kidney, brain or both? Trends Endocrinol Metab 2002; 13: 403–408.

    Article  CAS  PubMed  Google Scholar 

  77. Langley-Evans SC, Langley-Evans AJ, Marchand MC . Nutritional programming of blood pressure and renal morphology. Arch Physiol Biochem 2003; 111: 8–16.

    Article  CAS  PubMed  Google Scholar 

  78. Wintour EM, Johnson K, Koukoulas I, Moritz K, Tersteeg M, Dodic M . Programming the cardiovascular system, kidney and the brain—a review. Placenta 2003; 24 (Suppl A): S65–S71.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cell Biology, Institute of Life Science, Université Catholique de Louvain, Louvain-la-Neuve, Belgium

    C Remacle, F Bieswal & B Reusens

Authors
  1. C Remacle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Bieswal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Reusens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Remacle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Remacle, C., Bieswal, F. & Reusens, B. Programming of obesity and cardiovascular disease. Int J Obes 28 (Suppl 3), S46–S53 (2004). https://doi.org/10.1038/sj.ijo.0802800

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802800

Keywords

This article is cited by

Search

Advanced search

Quick links