Genes & Nutrition

, Volume 4, Issue 3, pp 189–194

Gene and protein expression profiles in the foetal liver of the pregnant rat fed a low protein diet

  • Christopher J. McNeil
  • Susan M. Hay
  • Garry J. Rucklidge
  • Martin D. Reid
  • Gary J. Duncan
  • William David Rees
Brief Communication

Abstract

Foetal growth is particularly sensitive to the protein content of the mother’s diet. Microarray data from the foetal liver of pregnant rats fed normal (HP) or reduced protein diets (LP) were compared by gene set enrichment analysis. Soluble proteins from a second portion of the liver were analysed by two-dimensional gel electrophoresis. Genes associated with progesterone, insulin-like growth factor-1 and vascular endothelial growth factor were upregulated in HP compared to LP, in addition to genes associated with cell differentiation and signalling from the extracellular matrix. In contrast, cytokine signalling was downregulated. Proteomics showed that proteins associated with amino acid metabolism, mitochondrial function and cell motility were differentially abundant in the HP compared to the LP groups. These growth factor and extracellular matrix signalling pathways linked to cell motility may be important mediators of the changes in liver structure that occur in utero and persist into adult life.

Keywords

Programming Hepatic development Metabolism Foetal origins of disease 

References

  1. 1.
    Avruch J, Long X, Ortiz-vega S, Rapley J, Papageorgiou A, Dai N (2009) Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab 296(4):E592–602PubMedCrossRefGoogle Scholar
  2. 2.
    Desai M, Crowther NJ, Ozanne SE, Lucas A, Hales CN (1995) Adult glucose and lipid metabolism may be programmed during fetal life. Biochem Soc Trans 23:331–335PubMedGoogle Scholar
  3. 3.
    El Khattabi I, Gregoire F, Remacle C, Reusens B (2003) Isocaloric maternal low-protein diet alters IGF-I, IGFBPs, and hepatocyte proliferation in the fetal rat. Am J Physiol Endocrinol Metab 285:E991–E1000PubMedGoogle Scholar
  4. 4.
    Fernandez-Twinn DS, Ozanne SE, Ekizoglou S, Doherty C, James L, Gusterson B, Hales CN (2003) The maternal endocrine environment in the low-protein model of intra-uterine growth restriction. Br J Nutr 90:815–822PubMedCrossRefGoogle Scholar
  5. 5.
    Gluckman PD, Hanson MA, Cooper C, Thornburg KL (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359:61–73PubMedCrossRefGoogle Scholar
  6. 6.
    Jousse C, Averous J, Bruhat A, Carraro V, Mordier S, Fafournoux P (2004) Amino acids as regulators of gene expression: molecular mechanisms. Biochem Biophys Res Commun 313:447–452PubMedCrossRefGoogle Scholar
  7. 7.
    Katz NR (1992) Metabolic heterogeneity of hepatocytes across the liver acinus. J Nutr 122:843–849PubMedGoogle Scholar
  8. 8.
    Krussel JS, Bielfeld P, Polan ML, Simon C (2003) Regulation of embryonic implantation. Eur J Obstet Gynecol Reprod Biol 110:S2–S9PubMedCrossRefGoogle Scholar
  9. 9.
    Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75:59–72PubMedGoogle Scholar
  10. 10.
    Lorenzo M, Roncero C, Benito M (1986) The role of prolactin and progesterone in the regulation of lipogenesis in maternal and foetal rat liver in vivo and in isolated hepatocytes during the last day of gestation. Biochem J 239:135–139PubMedGoogle Scholar
  11. 11.
    Maloney CA, Lilley C, Cruickshank M, McKinnon C, Hay SM, Rees WD (2005) The expression of growth-arrest genes in the liver and kidney of the protein-restricted rat fetus. Br J Nutr 94:12–18PubMedCrossRefGoogle Scholar
  12. 12.
    Maloney CA, Lilley C, Czopek A, Hay SM, Rees WD (2007) Interactions between protein and vegetable oils in the maternal diet determine the programming of the insulin axis in the rat. Br J Nutr 97:912–920PubMedCrossRefGoogle Scholar
  13. 13.
    McNeil CJ, Hay SM, Rucklidge G, Reid M, Duncan G, Maloney CA, Rees WD (2008) Disruption of lipid metabolism in the liver of the pregnant rat fed folate deficient and methyl donor deficient diets. Br J Nutr 99(2):262–271PubMedCrossRefGoogle Scholar
  14. 14.
    Owens JA (1991) Endocrine and substrate control of fetal growth: placental and maternal influences and insulin-like growth factors. Reprod Fertil Dev 3:501–517PubMedCrossRefGoogle Scholar
  15. 15.
    Rees WD, Hay SM, Buchan V, Antipatis C, Palmer RM (1999) The effects of maternal protein restriction on the growth of the rat fetus and its amino acid supply. Br J Nutr 81:243–250PubMedGoogle Scholar
  16. 16.
    Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP (2006) GenePattern 2.0. Nat Genet 38:500–501PubMedCrossRefGoogle Scholar
  17. 17.
    Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550PubMedCrossRefGoogle Scholar
  18. 18.
    Widdowson EM, McCance RA (1963) The effect of finite periods of undernutrition at different ages on the composition and subsequent development of the rat. Proc R Soc Lond B Biol Sci 158:329–342PubMedCrossRefGoogle Scholar
  19. 19.
    Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Christopher J. McNeil
    • 1
  • Susan M. Hay
    • 1
  • Garry J. Rucklidge
    • 1
  • Martin D. Reid
    • 1
  • Gary J. Duncan
    • 1
  • William David Rees
    • 1
  1. 1.Rowett Institute of Nutrition and HealthThe University of AberdeenAberdeenScotland, UK

Personalised recommendations