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

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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.

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Abbreviations

pGL3:

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

SREBP-1c:

Sterol response element binding protein

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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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Authors and Affiliations

  1. School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Aml Erhuma & Andrew J. Bennett

  2. School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD, UK

    Sarah McMullen & Simon C. Langley-Evans

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  1. Aml Erhuma
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  2. Sarah McMullen
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  3. Simon C. Langley-Evans
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  4. Andrew J. Bennett
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Correspondence to Aml Erhuma.

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Erhuma, A., McMullen, S., Langley-Evans, S.C. et al. Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism. Endocr 36, 333–338 (2009). https://doi.org/10.1007/s12020-009-9225-8

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  • DOI: https://doi.org/10.1007/s12020-009-9225-8

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