Skip to main content
SpringerLink
Log in

Maternal micronutrient restriction programs the body adiposity, adipocyte function and lipid metabolism in offspring: A review

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Fetal growth is a complex process which depends both on the genetic makeup and intrauterine environment. Maternal nutrition during pregnancy is an important determinant of fetal growth. Adequate nutrient supply is required during pregnancy and lactation for the support of fetal/infant growth and development. Macro- and micronutrients are both important to sustain pregnancy and for appropriate growth of the fetus. While macronutrients provide energy and proteins for fetal growth, micronutrients play a major role in the metabolism of macronutrients, structural and cellular metabolism of the fetus. Discrepancies in maternal diet at different stages of foetal growth / offspring development can have pronounced influences on the health and well-being of the offspring. Indeed intrauterine growth restriction induced by nutrient insult can irreversibly modulate the endocrine/metabolic status of the fetus that leads to the development of adiposity and insulin resistance in its later life. Understanding the role of micronutrients during the development of fetus will provide insights into the probable underlying / associated mechanisms in the metabolic pathways of endocrine related complications. Keeping in view the modernized lifestyle and food habits that lead to the development of adiposity and world burden of obesity, this review focuses mainly on the role of maternal micronutrients in the foetal origins of adiposity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bernstein I, Gabbe SG. Intrauterine growth restriction. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics: normal & problem pregnancies. 3rd ed. New York: Churchill Livingstone; 1996. p. 863–886.

  2. Eleftheriades M, Creatsas G, Nicolaides K. Fetal growth restriction and postnatal development. Ann N Y Acad Sci. 2006;1092:319–30.

    Article  PubMed  CAS  Google Scholar 

  3. Neerhof MG. Causes of intrauterine growth restriction. Clin Perinatol. 1995;22:375–85.

    PubMed  CAS  Google Scholar 

  4. Bryan SM, Hindmarsh PC. Normal and abnormal fetal growth. Horm Res. 2006;65 Suppl 3:19–27.

    Article  PubMed  CAS  Google Scholar 

  5. Fraser AM, Brockert JE, Ward RH. Association of young maternal age with adverse reproductive outcomes. N Engl J Med. 1995;332:1113–7.

    Article  PubMed  CAS  Google Scholar 

  6. Van Assche FA, De Prins F, Aerts L, Verjans M. The endocrine pancreas in small-for-dates infants. Br J Obstet Gynaecol. 1977;84:751–3.

    Article  PubMed  Google Scholar 

  7. Nicolini U, Hubinont C, Santolaya J, Fisk NM, Rodeck CH. Effects of fetal intravenous glucose challenge in normal and growth retarded fetuses. Horm Metab Res. 1990;22:426–30.

    Article  PubMed  CAS  Google Scholar 

  8. Barker DJ. In utero programming of chronic disease. Clin Sci (Lond). 1998;95:115–28.

    Article  CAS  Google Scholar 

  9. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter PD. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991;303:1019–22.

    Article  PubMed  CAS  Google Scholar 

  10. Jaquet D, Gaboriau A, Czernichow P, Levy-Marchal C. Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab. 2000;85:1401–6.

    Article  PubMed  CAS  Google Scholar 

  11. de Onis M, Blossner M, Villar J. Levels and patterns of intrauterine growth retardation in developing countries. Eur J Clin Nutr. 1998;52 Suppl 1:S5–S15.

    PubMed  Google Scholar 

  12. Pollack RN, Divon MY. Intrauterine growth retardation: definition, classification, and etiology. Clin Obstet Gynecol. 1992;35:99–107.

    Article  PubMed  CAS  Google Scholar 

  13. McAnarney ER. Young maternal age and adverse neonatal outcome. Am J Dis Child. 1987;141:1053–9.

    PubMed  CAS  Google Scholar 

  14. Adelson PL, Frommer MS, Pym MA, Rubin GL. Teenage pregnancy and fertility in New South Wales: an examination of fertility trends, abortion and birth outcomes. Aust J Public Health. 1992;16:238–44.

    Article  PubMed  CAS  Google Scholar 

  15. Cooper LG, Leland NL, Alexander G. Effect of maternal age on birth outcomes among young adolescents. Soc Biol. 1995;42:22–35.

    PubMed  CAS  Google Scholar 

  16. WHO/UNICEF. Low birthweight: country, regional and global estimates. New York, United Nations Children’s Fund and World Health Organization, 2004

  17. Abrams SA. In utero physiology: role in nutrient delivery and fetal development for calcium, phosphorus, and vitamin D. Am J Clin Nutr. 2007;85:604S–7S.

    PubMed  CAS  Google Scholar 

  18. UNICEF: Vitamin and mineral deficiencies: a global progress report. The Micronutrient Initiative and UNICEF, 2004 by Peter Adamson, P&LA, Oxfordshire, UK.

  19. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr. 2000;71:1295S–303S.

    PubMed  CAS  Google Scholar 

  20. Coursin DB. Vitamin B6 metabolism in infants and children. Vitam Horm. 1964;22:755–86.

    Article  PubMed  CAS  Google Scholar 

  21. Cederberg J, Siman CM, Eriksson UJ. Combined treatment with vitamin E and vitamin C decreases oxidative stress and improves fetal outcome in experimental diabetic pregnancy. Pediatr Res. 2001;49:755–62.

    Article  PubMed  CAS  Google Scholar 

  22. Siman CM, Eriksson UJ. Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats. Diabetologia. 1997;40:1416–24.

    Article  PubMed  CAS  Google Scholar 

  23. Raman L, Rajalakshmi K, Krishnamachari KA, Sastry JG. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the bone density of the neonates. Am J Clin Nutr. 1978;31:466–9.

    PubMed  CAS  Google Scholar 

  24. Koo WW, Walters JC, Esterlitz J, Levine RJ, Bush AJ, Sibai B. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol. 1999;94:577–82.

    Article  PubMed  CAS  Google Scholar 

  25. Linder MC. The biochemistry of copper. New York: Plenum Press; 1991.

    Google Scholar 

  26. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr. 2000;72:257S–64S.

    PubMed  CAS  Google Scholar 

  27. Krachler M, Rossipal E, Micetic-Turk D. Trace element transfer from the mother to the newborn–investigations on triplets of colostrum, maternal and umbilical cord sera. Eur J Clin Nutr. 1999;53:486–94.

    Article  PubMed  CAS  Google Scholar 

  28. Hurley LS. Developmental nutrition. Englewood Cliffs: Prentice-Hall; 1980.

    Google Scholar 

  29. Barker DJ. The fetal and infant origins of disease. Eur J Clin Invest. 1995;25:457–63.

    Article  PubMed  CAS  Google Scholar 

  30. Barker DJ. Intrauterine programming of adult disease. Mol Med Today. 1995;1:418–23.

    Article  PubMed  CAS  Google Scholar 

  31. Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE. Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999;84:137–44.

    Article  PubMed  CAS  Google Scholar 

  32. Deurenberg P, Deurenberg-Yap M, Guricci S. Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship. Obes Rev. 2002;3:141–6.

    Article  PubMed  CAS  Google Scholar 

  33. Yajnik CS. Early life origins of insulin resistance and type 2 diabetes in India and other Asian countries. J Nutr. 2004;134:205–10.

    PubMed  CAS  Google Scholar 

  34. Gilbert-Diamond D, Baylin A, Mora-Plazas M, Marin C, Arsenault JE, Hughes MD, Willett WC, Villamor E. Vitamin D deficiency and anthropometric indicators of adiposity in school-age children: a prospective study. Am J Clin Nutr. 2010;92:1446–51.

    Article  PubMed  CAS  Google Scholar 

  35. Dong Y, Pollock N, Stallmann-Jorgensen IS, Gutin B, Lan L, Chen TC, Keeton D, Petty K, Holick MF, Zhu H. Low 25-hydroxyvitamin D levels in adolescents: race, season, adiposity, physical activity, and fitness. Pediatrics. 2010;125:1104–11.

    Article  PubMed  Google Scholar 

  36. Krishnaveni GV, Hill JC, Veena SR, Bhat DS, Wills AK, Karat CL, Yajnik CS, Fall CH. Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes. Diabetologia. 2009;52:2350–8.

    Article  PubMed  CAS  Google Scholar 

  37. Zimmermann MB, Zeder C, Muthayya S, Winichagoon P, Chaouki N, Aeberli I, Hurrell RF. Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification. Int J Obes (Lond). 2008;32:1098–104.

    Article  CAS  Google Scholar 

  38. Venu L, Harishankar N, Krishna TP, Raghunath M. Does maternal dietary mineral restriction per se predispose the offspring to insulin resistance? Eur J Endocrinol. 2004;151:287–94.

    Article  PubMed  CAS  Google Scholar 

  39. Venu L, Harishankar N, Prasanna Krishna T, Raghunath M. Maternal dietary vitamin restriction increases body fat content but not insulin resistance in WNIN rat offspring up to 6 months of age. Diabetologia. 2004;47:1493–501.

    Article  PubMed  CAS  Google Scholar 

  40. Venu L, Kishore YD, Raghunath M. Maternal and perinatal magnesium restriction predisposes rat pups to insulin resistance and glucose intolerance. J Nutr. 2005;135:1353–8.

    PubMed  CAS  Google Scholar 

  41. Venu L, Padmavathi IJ, Kishore YD, Bhanu NV, Rao KR, Sainath PB, Ganeshan M, Raghunath M. Long-term effects of maternal magnesium restriction on adiposity and insulin resistance in rat pups. Obesity (Silver Spring). 2008;16:1270–6.

    Article  CAS  Google Scholar 

  42. Raghunath M, Venu L, Padmavathi I, Kishore YD, Ganeshan M, Anand Kumar K, Sainath PB, Rao KR. Modulation of macronutrient metabolism in the offspring by maternal micronutrient deficiency in experimental animals. Indian J Med Res. 2009;130:655–65.

    PubMed  CAS  Google Scholar 

  43. Padmavathi IJ, Kishore YD, Venu L, Ganeshan M, Harishankar N, Giridharan NV, Raghunath M. Prenatal and perinatal zinc restriction: effects on body composition, glucose tolerance and insulin response in rat offspring. Exp Physiol. 2009;94:761–9.

    Article  PubMed  CAS  Google Scholar 

  44. Padmavathi IJN, Rao KR, Venu L, Ganeshan M, Kumar KA, Rao Ch N, Harishankar N, Ismail A, Raghunath M: Chronic maternal dietary chromium restriction modulates visceral adiposity: probable underlying mechanisms. Diabetes. 2010;59:98–104.

    Article  PubMed  CAS  Google Scholar 

  45. Manisha Ganeshan SP, Padmavathi IJN, Venu L, Kishore YD, Anand K, Harishanker N, Srinivasa Rao J, Raghunath M (2011) Maternal manganese restriction increases susceptibility to high fat diet induced dyslipidemia and altered adipose function in WNIN male rat offspring. Exp Diabetes Res (In press)

  46. Anand Kumar K, Padmavathi IJN, Lalitha A, Manisha G, Rao KR, Mahesh Kumar J, Chandak GR, Raghunath M: Chronic maternal vitamin B12 restriction induced changes in the wistar rat offspring are partly correctable by rehabilitation (Abstract). CMR e-journal 2010

  47. Ribot J, Felipe F, Bonet ML, Palou A. Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression. Obes Res. 2001;9:500–9.

    Article  PubMed  CAS  Google Scholar 

  48. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999;4:611–7.

    Article  PubMed  CAS  Google Scholar 

  49. Horton JD, Shimomura I, Brown MS, Hammer RE, Goldstein JL, Shimano H. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2. J Clin Invest. 1998;101:2331–9.

    Article  PubMed  CAS  Google Scholar 

  50. Joss-Moore LA, Wang Y, Campbell MS, Moore B, Yu X, Callaway CW, McKnight RA, Desai M, Moyer-Mileur LJ, Lane RH. Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity. Early Hum Dev. 2010;86:179–85.

    Article  PubMed  CAS  Google Scholar 

  51. Desbriere R, Vuaroqueaux V, Achard V, Boullu-Ciocca S, Labuhn M, Dutour A, Grino M. 11beta-hydroxysteroid dehydrogenase type 1 mRNA is increased in both visceral and subcutaneous adipose tissue of obese patients. Obesity (Silver Spring). 2006;14:794–8.

    Article  CAS  Google Scholar 

  52. Boullu-Ciocca S, Achard V, Tassistro V, Dutour A, Grino M. Postnatal programming of glucocorticoid metabolism in rats modulates high-fat diet-induced regulation of visceral adipose tissue glucocorticoid exposure and sensitivity and adiponectin and proinflammatory adipokines gene expression in adulthood. Diabetes. 2008;57:669–77.

    Article  PubMed  CAS  Google Scholar 

  53. Jazet IM, Pijl H, Meinders AE. Adipose tissue as an endocrine organ: impact on insulin resistance. Neth J Med. 2003;61:194–212.

    PubMed  CAS  Google Scholar 

  54. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–56.

    Article  PubMed  CAS  Google Scholar 

  55. Fontbonne A, Eschwege E, Cambien F, Richard JL, Ducimetiere P, Thibult N, Warnet JM, Claude JR, Rosselin GE. Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 11-year follow-up of the Paris Prospective Study. Diabetologia. 1989;32:300–4.

    Article  PubMed  CAS  Google Scholar 

  56. Smith U. Impaired ('diabetic') insulin signaling and action occur in fat cells long before glucose intolerance–is insulin resistance initiated in the adipose tissue? Int J Obes Relat Metab Disord. 2002;26:897–904.

    Article  PubMed  CAS  Google Scholar 

  57. Koo SI, Norvell JE, Algilani K, Chow J. Effect of marginal zinc deficiency on the lymphatic absorption of [14C]cholesterol. J Nutr. 1986;116:2363–71.

    PubMed  CAS  Google Scholar 

  58. Kim ES, Noh SK, Koo SI. Marginal zinc deficiency lowers the lymphatic absorption of alpha-tocopherol in rats. J Nutr. 1998;128:265–70.

    PubMed  CAS  Google Scholar 

  59. LeBlanc CP, Fiset S, Surette ME, Turgeon O'Brien H, Rioux FM. Maternal iron deficiency alters essential fatty acid and eicosanoid metabolism and increases locomotion in adult guinea pig offspring. J Nutr. 2009;139:1653–9.

    Article  PubMed  CAS  Google Scholar 

  60. Crowe C, Dandekar P, Fox M, Dhingra K, Bennet L, Hanson MA. The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats. J Physiol. 1995;488(Pt 2):515–9.

    PubMed  CAS  Google Scholar 

  61. Lewis RM, Petry CJ, Ozanne SE, Hales CN. Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring. Metabolism. 2001;50:562–7.

    Article  PubMed  CAS  Google Scholar 

  62. Singla PN, Tyagi M, Kumar A, Dash D, Shankar R. Fetal growth in maternal anaemia. J Trop Pediatr. 1997;43:89–92.

    Article  PubMed  CAS  Google Scholar 

  63. Zhang J, Lewis RM, Wang C, Hales N, Byrne CD. Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses. Am J Physiol Regul Integr Comp Physiol. 2005;288:R104–11.

    Article  PubMed  CAS  Google Scholar 

  64. Kwik-Uribe CL, Gietzen D, German JB, Golub MS, Keen CL. Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism and myelin composition. J Nutr. 2000;130:2821–30.

    PubMed  CAS  Google Scholar 

  65. 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;127:4195–202.

    PubMed  CAS  Google Scholar 

  66. Brawley L, Itoh S, Torrens C, Barker A, Bertram C, Poston L, Hanson M. Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring. Pediatr Res. 2003;54:83–90.

    Article  PubMed  CAS  Google Scholar 

  67. Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004;20:63–8.

    Article  PubMed  CAS  Google Scholar 

  68. Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG. Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis. 2006;44:401–6.

    Article  PubMed  CAS  Google Scholar 

  69. Fu Q, McKnight RA, Yu X, Wang L, Callaway CW, Lane RH. Uteroplacental insufficiency induces site-specific changes in histone H3 covalent modifications and affects DNA-histone H3 positioning in day 0 IUGR rat liver. Physiol Genomics. 2004;20:108–16.

    Article  PubMed  CAS  Google Scholar 

  70. Razin A. CpG methylation, chromatin structure and gene silencing-a three-way connection. EMBO J. 1998;17:4905–8.

    Article  PubMed  CAS  Google Scholar 

  71. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005;135:1382–6.

    PubMed  CAS  Google Scholar 

  72. Jackson AA, Dunn RL, Marchand MC, Langley-Evans SC. Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Clin Sci (Lond). 2002;103:633–9.

    CAS  Google Scholar 

  73. Brawley L, Torrens C, Anthony FW, Itoh S, Wheeler T, Jackson AA, Clough GF, Poston L, Hanson MA. Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy. J Physiol. 2004;554:497–504.

    Article  PubMed  CAS  Google Scholar 

  74. Gallou-Kabani C, Junien C. Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic. Diabetes. 2005;54:1899–906.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, National Institute of Nutrition, Jamai Osmania P O, Hyderabad, 500 007, India

    K. Rajender Rao, I. J. N. Padmavathi & M. Raghunath

  2. National Center for Laboratory Animal Sciences, National Institute of Nutrition, Hyderabad, 500 007, India

    K. Rajender Rao

Authors
  1. K. Rajender Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. J. N. Padmavathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Raghunath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Raghunath.

Additional information

All the authors contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rao, K.R., Padmavathi, I.J.N. & Raghunath, M. Maternal micronutrient restriction programs the body adiposity, adipocyte function and lipid metabolism in offspring: A review. Rev Endocr Metab Disord 13, 103–108 (2012). https://doi.org/10.1007/s11154-012-9211-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-012-9211-y

Keywords

Search

Navigation