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JCI table of contents, 17 May 2004

this relationship is unknown. Johan Auwerx and collaborators, from Institut de Genetique et Biologie Moleculaire et Cellulaire, traced this elusive pathway through experiments with a diet-inducible hypertriglyceridemic mouse model and showed that bile acidrelated TG level reduction occurs through transcriptional regulation. TG levels were significantly lowered in mice receiving either a natural or a synthetic agonist for the bile acid receptor FXR. Mice treated with cholic acid, a type of bile acid, also had increased SHP expression levels. SHP, an FXR target, represses the nuclear receptor LXR. LXR is essential for a basal transcription level of SREBP-1c. The authors analyzed the SREBP-1c promoter using luciferase assays to show that SREBP-1c expression was attenuated via the FXR/SHP cascade. Finally, SHP/ mice as well as LXR_/_/ mice showed no decrease in TG levels upon cholic acid treatment, further supporting this transcription pathway as the link between bile acid presence and TG levels.

TITLE: Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c

AUTHOR CONTACT:
Johan Auwerx
Institut de Genetique et Biologie Moleculaire et Cellulaire, Illkirch, France.
Phone: 33-38-865-3425; Fax: 33-3-8865-3201; E-mail: auwerx@igbmc.u-strasbg.fr

View the PDF of this article at: https://www.the-jci.org/press/21025.pdf

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Pancreatic Maturity Lost with E2F Loss

The E2F transcription factor family is known to be important in regulating cell growth and differentiation. Phenotypes of single- and double-mutant mice of the six gene family members display varied defects in systemic and cellular function. Ana Zubiaga and colleagues, from the University of the Basque Country, previously characterized E2F1 and E2F2 single-knockout mice and con
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Contact: Laurie Goodman
press_releases@the-jci.org
212-342-4159
Journal of Clinical Investigation
17-May-2004


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