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Endocrine

, Volume 36, Issue 2, pp 333–338 | Cite as

Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism

  • Aml Erhuma
  • Sarah McMullen
  • Simon C. Langley-Evans
  • Andrew J. Bennett
Original Article

Abstract

Prenatal exposure to a low-protein diet programmes altered expression of genes that regulate lipid metabolism, including SREBP-1c. The main aim of this study was to investigate whether programmed changes to hepatic SREBP-1c expression in the rat are glucocorticoid-dependent. Rats were fed isocaloric diets (control or low-protein) throughout pregnancy. The low-protein group received 11β-hydroxylase inhibitor, the inhibitor plus corticosterone, or vehicle injections over the first 2 weeks of pregnancy. The control group was administered vehicle injections only. On delivery the animals were transferred to a standard chow diet. The offspring were weaned at 4 weeks of age on to the same chow diet and killed for collection of liver tissue. The inhibitor of glucocorticoid synthesis reversed the suppressive effect of low-protein diet on hepatic SREBP-1c expression of both protein and mRNA seen in low-protein exposed offspring. To test if this effect is through direct effect on the SREBP-1c promoter, H4IIE cells were transfected with a luciferase reporter construct controlled by the SREBP-1c promoter treated with dexamethasone. Dexamethasone induced the expression of SREBP-1c in vitro. Together these studies demonstrate that foetal over-exposure to glucocorticoids, through indirect mechanism, play a crucial role in low-protein-diet-induced changes in lipid metabolism regulating genes.

Keywords

Prenatal programming SREBP-1c Glucocorticoids 

Abbreviations

pGL3

pGL3-basic vector; pSREBP1c; SREBP-1c promoter

SREBP-1c

Sterol response element binding protein

Notes

Acknowledgements

The animal studies described in this work were funded by the British Heart Foundation. Aml Erhuma was funded by a scholarship from the Libyan Government.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Aml Erhuma
    • 1
  • Sarah McMullen
    • 2
  • Simon C. Langley-Evans
    • 2
  • Andrew J. Bennett
    • 1
  1. 1.School of Biomedical SciencesUniversity of Nottingham, Queen’s Medical CentreNottinghamUK
  2. 2.School of BiosciencesUniversity of Nottingham, Sutton BoningtonLoughboroughUK

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