A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver

Hiromi Yamashita, Makoto Takenoshita, Masaharu Sakurai, Richard K. Bruick, William J. Henzel, Wendy Shillinglaw, David Arnot, Kosaku Uyeda

Research output: Contribution to journalArticle

454 Scopus citations

Abstract

Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity in vitro precisely correlates with promoter activity in vivo. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.

Original languageEnglish (US)
Pages (from-to)9116-9121
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number16
DOIs
StatePublished - Jul 31 2001

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Yamashita, H., Takenoshita, M., Sakurai, M., Bruick, R. K., Henzel, W. J., Shillinglaw, W., Arnot, D., & Uyeda, K. (2001). A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proceedings of the National Academy of Sciences of the United States of America, 98(16), 9116-9121. https://doi.org/10.1073/pnas.161284298