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Originally published In Press as doi:10.1074/jbc.M212846200 on December 17, 2002

J. Biol. Chem., Vol. 278, Issue 9, 6959-6962, February 28, 2003
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Selective Proteolytic Processing of Rat Hepatic Sterol Regulatory Element Binding Protein-1 (SREBP-1) and SREBP-2 During Postnatal Development*

Daniela Botolin and Donald B. JumpDagger

From the Departments of Physiology, Biochemistry, and Molecular Biology, Michigan State University, East Lansing, Michigan 48824

Sterol regulatory element-binding protein-1c (SREBP-1c) plays a major role in hepatic lipogenic gene expression. In adult animals, insulin and oxysterols induce SREBP-1c gene transcription, whereas polyunsaturated fatty acids suppress the nuclear content of SREBP-1c through pre-translational regulatory mechanisms. A decline in nuclear SREBP-1 is associated with suppression of hepatic lipogenesis. In contrast to adult rats, hepatic lipogenesis in preweaned neonatal rats is low. Ingestion of milk fat by the neonate may contribute to low hepatic lipogenesis. In this report, we tested the hypothesis that low lipogenic gene expression prior to weaning correlates with low mRNASREBP-1c, as well as low precursor and nuclear forms of SREBP-1. In contrast to expectations, levels of mRNASREBP-1c and the 125-kDa SREBP-1 precursor in livers of preweaned rats was comparable with adult levels. Despite high levels of SREBP-1 precursor, mature (65 kDa) SREBP-1 was not detected in rat liver nuclei prior to 18 days postpartum. Weaning rats at 21 days postpartum was accompanied by a rise in nuclear SREBP-1 levels as well as increased lipogenic gene expression. In contrast, SREBP-2 was present in rat liver nuclei, and its target gene, HMG-CoA reductase, was expressed above adult levels prior to weaning. These studies indicate that, prior to weaning, SREBP-2 but not SREBP-1 is proteolytically processed to the mature form. As such, SREBP-2-regulated genes are active. Failure of SREBP-1 to be processed to the mature form <18 days postpartum correlates with low hepatic lipogenic gene expression. This mechanism differs from the hormonal and fatty acid-mediated pre-translational control of SREBP-1c in adult liver.

* This research was supported by National Institutes of Health Grant DK43220, United States Department of Agriculture Grant 98-35200-6064, and the Michigan Agriculture Experiment Station.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Physiology, 3165 Biomedical and Physical Science Bldg., Michigan State University, East Lansing, MI 48824. Tel.: 517-355-6475 (ext. 1246); Fax: 517-355-5125; E-mail: Jump@msu.edu.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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