Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism.
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 11beta-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.
Erhuma
Aml
A
School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK. aml_erhuma@yahoo.co.uk
McMullen
Sarah
S
Langley-Evans
Simon C
SC
Bennett
Andrew J
AJ
D000315:Adrenalectomy / Q000379:methods; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena; D008797:Metyrapone / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
D004044:Dietary Proteins; D005938:Glucocorticoids; D051780:Sterol Regulatory Element Binding Protein 1; D003907:Dexamethasone; D008797:Metyrapone