CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-γ

Stephan Herzig, Susan Hedrick, Ianessa Morantte, Seung-Hoi Koo, Francesco Galimi and Marc Montminy ()
Additional contact information
Stephan Herzig: Peptide Biology Laboratories Salk Institute for Biological Studies
Susan Hedrick: Peptide Biology Laboratories Salk Institute for Biological Studies
Ianessa Morantte: Peptide Biology Laboratories Salk Institute for Biological Studies
Seung-Hoi Koo: Peptide Biology Laboratories Salk Institute for Biological Studies
Francesco Galimi: Laboratory of Genetics, Salk Institute for Biological Studies
Marc Montminy: Peptide Biology Laboratories Salk Institute for Biological Studies

Nature, 2003, vol. 426, issue 6963, 190-193

Abstract: Abstract Fasting triggers a series of hormonal cues that promote energy balance by inducing glucose output and lipid breakdown in the liver1. In response to pancreatic glucagon and adrenal cortisol, the cAMP-responsive transcription factor CREB activates gluconeogenic and fatty acid oxidation programmes by stimulating expression of the nuclear hormone receptor coactivator PGC-1 (refs 2–5). In parallel, fasting also suppresses lipid storage and synthesis (lipogenic) pathways1, but the underlying mechanism is unknown. Here we show that mice deficient in CREB activity have a fatty liver phenotype and display elevated expression of the nuclear hormone receptor PPAR-γ, a key regulator of lipogenic genes6,7. CREB inhibits hepatic PPAR-γ expression in the fasted state by stimulating the expression of the Hairy Enhancer of Split (HES-1) gene, a transcriptional repressor that is shown here to be a mediator of fasting lipid metabolism in vivo. The coordinate induction of PGC-1 and repression of PPAR-γ by CREB during fasting provides a molecular rationale for the antagonism between insulin and counter-regulatory hormones, and indicates a potential role for CREB antagonists as therapeutic agents in enhancing insulin sensitivity in the liver.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature02110 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:426:y:2003:i:6963:d:10.1038_nature02110

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02110

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().