Glucose and Insulin Function through Two Distinct Transcription Factors to Stimulate Expression of Lipogenic Enzyme Genes in Liver

Seung Hoi Koo, Angela K. Dutcher, Howard C. Towle

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Transcription of a number of genes involved in lipogenesis is stimulated by dietary carbohydrate in the mammalian liver. Both insulin and increased glucose metabolism have been proposed to be initiating signals for this process, but the pathways by which these effectors act to alter transcription have not been resolved. We have previously defined by electrophoretic mobility shift assay a factor in nuclear extracts from rat liver, designated the carbohydrate-responsive factor (ChoRF), that binds to liver-type pyruvate kinase and S14 promoters at sites critical for regulation by carbohydrate. The sterol regulatory element binding protein-1c (SREBP-1c) has also emerged as a major transcription factor involved in this nutritional response. In this study, we examined the relationship between SREBP-1c and ChoRF in lipogenic gene induction. The two factors were found to possess distinct DNA binding specificities both in vitro and in hepatocytes. Reporter constructs containing binding sites for ChoRF were responsive to glucose but not directly to insulin. On the other hand, reporter constructs with an SREBP-1c site responded directly to insulin. The S14 gene possesses binding sites for both ChoRF and SREBP, and both sites were found to be functionally important for the response of this promoter to glucose and insulin in hepatocytes. Consequently, we propose that SREBP-1c and ChoRF are independent transcription factors that mediate signals generated by insulin and glucose, respectively. For many lipogenic enzyme genes, these two factors may provide an integrated signaling system to support the overall nutritional response to dietary carbohydrate.

Original languageEnglish
Pages (from-to)9437-9445
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number12
DOIs
Publication statusPublished - 2001 Mar 23

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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