Foxo1 Links Insulin Signaling to C/EBPalpha and Regulates Gluconeogenesis During Liver Development

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2007 Jul 14

PMID 17627282

Citations 26

Authors

Keisuke Sekine

Yen-Rong Chen

Nobuhiko Kojima

Kazuhiro Ogata

Akiyoshi Fukamizu

Atsushi Miyajima

Affiliations

Soon will be listed here.

Abstract

C/EBPalpha is a key transcription factor indispensable for the onset of gluconeogenesis in perinatal liver. However, C/EBPalpha was already expressed in fetal liver, suggesting that the expression of C/EBPalpha alone does not account for the dramatic increase of the expression of metabolic genes, and hence an additional factor(s) is expected to function cooperatively with C/EBPalpha in perinatal liver. We show here that expression of Foxo1 was sharply increased in the perinatal liver and augmented C/EBPalpha-dependent transcription. Foxo1 bound C/EBPalpha via its forkhead domain, and Foxo1 bound to the promoter of a gluconeogenic gene, phosphoenolpyruvate carboxykinase (PEPCK), in a C/EBPalpha-dependent manner in vivo. Insulin inhibited the expression of PEPCK in a culture of fetal liver cells, and also the C/EBPalpha-dependent transcription enhanced by Foxo1. These results indicate that Foxo1 regulates gluconeogenesis cooperatively with C/EBPalpha, and also links insulin signaling to C/EBPalpha during liver development.

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