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

  • K. Rajender Rao
  • I. J. N. Padmavathi
  • M. RaghunathEmail author
Article

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.

Keywords

Fetal programming Adiposity Micronutrients Maternal undernutrition Body fat% Adiposity index 

References

  1. 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.Google Scholar
  2. 2.
    Eleftheriades M, Creatsas G, Nicolaides K. Fetal growth restriction and postnatal development. Ann N Y Acad Sci. 2006;1092:319–30.PubMedCrossRefGoogle Scholar
  3. 3.
    Neerhof MG. Causes of intrauterine growth restriction. Clin Perinatol. 1995;22:375–85.PubMedGoogle Scholar
  4. 4.
    Bryan SM, Hindmarsh PC. Normal and abnormal fetal growth. Horm Res. 2006;65 Suppl 3:19–27.PubMedCrossRefGoogle Scholar
  5. 5.
    Fraser AM, Brockert JE, Ward RH. Association of young maternal age with adverse reproductive outcomes. N Engl J Med. 1995;332:1113–7.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 8.
    Barker DJ. In utero programming of chronic disease. Clin Sci (Lond). 1998;95:115–28.CrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 12.
    Pollack RN, Divon MY. Intrauterine growth retardation: definition, classification, and etiology. Clin Obstet Gynecol. 1992;35:99–107.PubMedCrossRefGoogle Scholar
  13. 13.
    McAnarney ER. Young maternal age and adverse neonatal outcome. Am J Dis Child. 1987;141:1053–9.PubMedGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Cooper LG, Leland NL, Alexander G. Effect of maternal age on birth outcomes among young adolescents. Soc Biol. 1995;42:22–35.PubMedGoogle Scholar
  16. 16.
    WHO/UNICEF. Low birthweight: country, regional and global estimates. New York, United Nations Children’s Fund and World Health Organization, 2004Google Scholar
  17. 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.PubMedGoogle Scholar
  18. 18.
    UNICEF: Vitamin and mineral deficiencies: a global progress report. The Micronutrient Initiative and UNICEF, 2004 by Peter Adamson, P&LA, Oxfordshire, UK. Google Scholar
  19. 19.
    Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr. 2000;71:1295S–303S.PubMedGoogle Scholar
  20. 20.
    Coursin DB. Vitamin B6 metabolism in infants and children. Vitam Horm. 1964;22:755–86.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 25.
    Linder MC. The biochemistry of copper. New York: Plenum Press; 1991.Google Scholar
  26. 26.
    Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr. 2000;72:257S–64S.PubMedGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Hurley LS. Developmental nutrition. Englewood Cliffs: Prentice-Hall; 1980.Google Scholar
  29. 29.
    Barker DJ. The fetal and infant origins of disease. Eur J Clin Invest. 1995;25:457–63.PubMedCrossRefGoogle Scholar
  30. 30.
    Barker DJ. Intrauterine programming of adult disease. Mol Med Today. 1995;1:418–23.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.CrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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)Google Scholar
  46. 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 2010Google Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 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.CrossRefGoogle Scholar
  52. 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.PubMedCrossRefGoogle Scholar
  53. 53.
    Jazet IM, Pijl H, Meinders AE. Adipose tissue as an endocrine organ: impact on insulin resistance. Neth J Med. 2003;61:194–212.PubMedGoogle Scholar
  54. 54.
    Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–56.PubMedCrossRefGoogle Scholar
  55. 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.PubMedCrossRefGoogle Scholar
  56. 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.PubMedCrossRefGoogle Scholar
  57. 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.PubMedGoogle Scholar
  58. 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.PubMedGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. 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.PubMedCrossRefGoogle Scholar
  62. 62.
    Singla PN, Tyagi M, Kumar A, Dash D, Shankar R. Fetal growth in maternal anaemia. J Trop Pediatr. 1997;43:89–92.PubMedCrossRefGoogle Scholar
  63. 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.PubMedCrossRefGoogle Scholar
  64. 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.PubMedGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. 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.PubMedCrossRefGoogle Scholar
  67. 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.PubMedCrossRefGoogle Scholar
  68. 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.PubMedCrossRefGoogle Scholar
  69. 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.PubMedCrossRefGoogle Scholar
  70. 70.
    Razin A. CpG methylation, chromatin structure and gene silencing-a three-way connection. EMBO J. 1998;17:4905–8.PubMedCrossRefGoogle Scholar
  71. 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.PubMedGoogle Scholar
  72. 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.Google Scholar
  73. 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.PubMedCrossRefGoogle Scholar
  74. 74.
    Gallou-Kabani C, Junien C. Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic. Diabetes. 2005;54:1899–906.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • K. Rajender Rao
    • 1
    • 2
  • I. J. N. Padmavathi
    • 1
  • M. Raghunath
    • 1
    Email author
  1. 1.Division of Endocrinology and MetabolismNational Institute of NutritionHyderabadIndia
  2. 2.National Center for Laboratory Animal SciencesNational Institute of NutritionHyderabadIndia

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