Endocrine

, Volume 14, Issue 3, pp 375–382 | Cite as

Impact of maternal undernutrition on hypothalamo-pituitary-adrenal axis and adipocyte functions in male rat offspring

  • Andrea N. Chisari
  • Andres Giovambattista
  • Mario Perello
  • Eduardo Spinedi
Article

Abstract

Malnutrition induces profound deleterious effects on several metabolic and neuroendocrine functions. In the present study, we examined the impact of maternal food restriction, during gestation and lactation, on the metabolic-neuroendocrine function of their male offspring at 21 and 60 d of age. Well-nourished (WN) and undernourished (UN) pregnant rats were used, during gestation and lactation, until pups were weaned. Twenty-one-day-old WN and UN male pups were studied in basal and postinsulin conditions. Additional groups of weaned (WN and UN) male rats were fed either ad libitum (WN-WN and UN-WN) or in a restricted fashion (WN-UN and UN-UN) until experimentation at age 60 d. Body weights of mothers and their male offspring were monitored. Basal and post-insulin plasma concentrations of several metabolic fuels were evaluated. Our results indicate that 21-d-old UN male rats exhibited (vs their WN counterparts), decreased body weights, similar basal and postinsulin glycemia, similar basal plasma adrenocorticotropic hormone (ACTH) and corticosterone levels but diminished ACTH response to insulin treatment, and basal hypoleptinemia and significant insulin-induced leptin release. Finally, at 60 d of age, long-term UN (WN-UN and UN-UN) rats showed lower plasma (basal and postinsulin) glucose, and basal triglyceride levels than their counterparts (WN-WN and UN-WN). Sixty-day-old rats submitted to either food restriction protocol also showed a reduced hypothalamo-pituitary-adrenalaxis response to insulin-induced hypoglycemia and basal hypoleptinemia, in spite of restoration of normal body weights. These results further indicate a clear metabolic-neuroendocrine dysfunction in male pups of UN mothers, with the abnormality partially present at weaning and deteriorated by adulthood, even after the recovery of normal body weight. Our study strongly supports the importance of the irreversibility of a deleterious allostatic state resulting from fetal and early postnatal undernutrition.

Key Words

Adrenocorticotropic hormone glucocorticoid carbohydrate leptin foodrestriction 

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References

  1. 1.
    Fauzi, W., Herrera, G., Spiegelman, D., ElAmin, A., Nestel, P., and Mohamed, K. (1997). Am. J. Clin. Nutr. 65, 1002–1009.Google Scholar
  2. 2.
    Zaman, K., Baqui, A., Yunus, M., Sack, R., Chowdhury, H., and Black, R. (1997). Acta Paediatr. 86, 923–927.PubMedGoogle Scholar
  3. 3.
    Jacobson, L., Zurakowski, D., and Majzoub, J. A. (1997). Endocrinology 138, 1048–1057.PubMedCrossRefGoogle Scholar
  4. 4.
    Giovambattista, A., Chisari, A. N., Corró, L., Gaillard, R. C., and Spinedi, E. (2000). Neuroimmunomodulation 7, 92–98.PubMedCrossRefGoogle Scholar
  5. 5.
    Suttmann, U., Selberg, O., Gallati, H., Ockenga, J., Deicher, H., and Muller, M. J. (1994). Clin. Sci. 86, 461–467.PubMedGoogle Scholar
  6. 6.
    Doherty, J. F., Golden, M. H. N., Raynes, J. G., Griffin, G. E., and McAdam, K. P. W. J. (1993). Clin. Sci. 84, 169–175.PubMedGoogle Scholar
  7. 7.
    Smith, S. R., Bledsoe, T., and Chhetri, M. K. (1975). J. Clin. Endocrinol. Metab. 40, 43–52.PubMedGoogle Scholar
  8. 8.
    Pimstone, B. (1976). Clin. Endocrinol. (Oxf.) 5, 79–95.Google Scholar
  9. 9.
    Bronson, F. H. (1986). Endocrinology 118, 2483–2487.PubMedCrossRefGoogle Scholar
  10. 10.
    Gruaz, N. M., Pierroz, D. D., Rohner-Jeanrenaud, F., Sizonenko, P. C., and Aubert, M. L. (1993). Endocrinology 133, 1891–1894.PubMedCrossRefGoogle Scholar
  11. 11.
    Hawkins, P., Steyn, C., McGarrigle, H. H., Saito, T., Ozaki, T., Stratford, L. L., Noakes, D. E., and Hanson, M. A. (2000). Exp. Physiol. 85, 85–96.PubMedCrossRefGoogle Scholar
  12. 12.
    Alvarez, C., Martin, M. A., Goya, L., Bertin, E., Portha, B., and Pascual-Leone, A. M. (1997). Endocrinology 138, 2267–2273.PubMedCrossRefGoogle Scholar
  13. 13.
    Wilson, M. R. and Hughes, S. J. (1997). J. Endocrinol. 154, 177–185.PubMedCrossRefGoogle Scholar
  14. 14.
    Frederich, R. C., Hamann, A., Anderson, S., Lollman, B., Lowell, B. B., and Flier, J. S. (1995). Nat. Med. 1, 1311–1314.PubMedCrossRefGoogle Scholar
  15. 15.
    Xu, B., Kalra, P. S., Farmerie, W. G., and Kalra, S. P. (1999). Endocrinology 140, 2868–2875.PubMedCrossRefGoogle Scholar
  16. 16.
    Chisari, A. N., Giovambattista, A., Suescun, M., and Spinedi E. (1999). Proceedings from the 81st Annual Meeting of the Endocrine Society, San Diego, CA (abstract).Google Scholar
  17. 17.
    Aird, F., Halasz, I., and Redei, E. (1997). Alcohol Clin. Exp. Res. 21, 1560–1566.PubMedGoogle Scholar
  18. 18.
    Cusin, I., Sainsbury, A., Doyle, P., Rohner-Jeanrenaud, F., and Jeanrenaud, B. (1995). Diabetes 44, 1467–1470.PubMedCrossRefGoogle Scholar
  19. 19.
    Saladin, R., De Vos, P., Guerre-Millo, M., Leturque, A., Girard, J., Staels, B., and Auwerx, J. (1995). Nature 377, 527–529.PubMedCrossRefGoogle Scholar
  20. 20.
    Dahri, S., Snoeck, A., Reusens-Billen, B., Remacle, C., and Hoet, J. J. (1991). Diabetes 40 (Suppl. 2), 115–120.PubMedGoogle Scholar
  21. 21.
    Kalra, S. P., Dube, M. G., Pu, S., Xu, B., Horvath, T. L., and Kalra, P. S. (1999). Endocr. Rev. 20, 68–100.PubMedCrossRefGoogle Scholar
  22. 22.
    Woods, S. C., Seeley, R. J., Porte, D. Jr., and Schwartz, M. W. (1998). Science 280, 1378–1382.PubMedCrossRefGoogle Scholar
  23. 23.
    Picarel-Blanchot, F., Alvarez, C., Bailbe, D., Pascual-Leone, A. M., and Portha, B. (1995). Metabolism 44, 1519–1526.PubMedCrossRefGoogle Scholar
  24. 24.
    McEwen, B. S. (1998). Ann. NY Acad. Sci. 840, 33–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Stokkan, K. A., Reiter, R. J., Vaughan, M. K., Nonaka, N. O., and Lerchl, A. (1991). Acta Endocrinol. (Copenh.) 125, 93–100.Google Scholar
  26. 26.
    Richard, D. (1993). Ann. NY Acad. Sci. 697, 155–172.PubMedCrossRefGoogle Scholar
  27. 27.
    Vale, W., Spiess, J., Rivier, C., and Rivier, J. (1981). Science 213, 1394–1397.PubMedCrossRefGoogle Scholar
  28. 28.
    Brady, L. S., Smith, M. A., Gold, P. W., and Herkenham, M. (1990). Neuroendocrinology 52, 441–447.PubMedGoogle Scholar
  29. 29.
    Timofeeva, E. and Richard, D. (1997). Neuroendocrinology 66, 327–340.PubMedGoogle Scholar
  30. 30.
    Bale, T. L., Contarino, A., Smith, G. W., Chan, R., Gold, L. H., Sawchenko, P. E., Koob, G. F., Vale, W. W., and Lee, K.-F. (2000). Nat. Genet. 24, 410–414.PubMedCrossRefGoogle Scholar
  31. 31.
    Pazzoli, G., Bilezikjian, L. M., Perrin, M. H., Blount, A. L., and Vale, W. W. (1996). Endocrinology 137, 65–71.CrossRefGoogle Scholar
  32. 32.
    Bradbury, M. J., McBurnie, M. I., Denton, D. A., Lee, K.-F., and Vale, W. W. (2000). Endocrinology 141, 2715–2724.PubMedCrossRefGoogle Scholar
  33. 33.
    Antoni, F. A. (1993). Front. Neuroendocrinol. 14, 76–122.PubMedCrossRefGoogle Scholar
  34. 34.
    Guillon, G., Trueba, M., Jourbet, D., Grazzini, E., Chouinard, L., Cote, M., Payet, M. D., Manzoni, O., Barberis, C., Robert, M., and Gallo-Payet, N. (1995). Endocrinology 136, 1285–1295.PubMedCrossRefGoogle Scholar
  35. 35.
    Muller, M. B., Landgraf, R., Preil, J., Sillaber, I., Kresse, A. E., Keck, M. E., Zimmermann, S., Holsboer, F., and Wurst, W. (2000). Endocrinology 141, 4262–4269.PubMedCrossRefGoogle Scholar
  36. 36.
    Tannenbaum, B. M., Tannenbaum, G. S., Brindley, D. N., Dallman, M. F., McArthur, M. D., and Meaney, M. J. (1997). Am. J. Physiol. 273, E1168-E1177.PubMedGoogle Scholar
  37. 37.
    Brindley, D. N., Cooling, J., Glenny, H. P., Burditt, S. L., McKechie, I. S. (1981). Biochem. J. 200, 275–284.PubMedGoogle Scholar
  38. 38.
    Nicholas, K. R. and Hartmann, P. E. (1991). Comp. Biochem. Physiol. 98A, 535–542.CrossRefGoogle Scholar
  39. 39.
    Trottier, G., Koski, K. G., Brun, T., Toufexis, D. J., Richard, D., and Walker, C.-D. (1998). Endocrinology 139, 3704–3711.PubMedCrossRefGoogle Scholar
  40. 40.
    Sapolsky, R. M., Romero, M., and Munck, A. U. (2000). Endocr. Rev. 21, 55–89.PubMedCrossRefGoogle Scholar
  41. 41.
    Spinedi, E., Hadid, R., and Gaillard, R. C. (1997). Neuroendocrinology 66, 287–93.PubMedGoogle Scholar
  42. 42.
    Chisari, A., Spinedi, E., Voirol, M.-J., Giovambattista, A., and Gaillard, R. C. (1998). Endocrinology 139, 617–625.PubMedCrossRefGoogle Scholar
  43. 43.
    Spinedi, E., Giacomini, M., Jacquier, M.w-C., and Gaillard, R. C. (1991). Neuroendocrinology 53, 160–170.PubMedGoogle Scholar
  44. 44.
    McElroy, W. D. and Swanson, C. P., eds. (1974). Biostatistical Analysis. Prentice-Hall, Englewood Cliffs, NJ.Google Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Andrea N. Chisari
    • 1
    • 2
  • Andres Giovambattista
    • 1
    • 2
  • Mario Perello
    • 1
  • Eduardo Spinedi
    • 1
  1. 1.Neuroendocrine Unit, Multidisciplinary Institute on Cell BiologyCONICET-CICLa PlataArgentina
  2. 2.School of Exact SciencesUNLPLa PlataArgentina

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