Intestine-specific deletion of SIRT1 in mice impairs DCoH2-HNF-1α-FXR signaling and alters systemic bile acid homeostasis.

ABSTRACT:

Background & aims

Sirtuin 1 (SIRT1), the most conserved mammalian oxidized nicotinamide adenine dinucleotide-dependent protein deacetylase, is an important metabolic sensor in many tissues. However, little is known about its role in the small intestine, which absorbs and senses nutrients. We investigated the functions of intestinal SIRT1 in systemic bile acid and cholesterol metabolism in mice.

Methods

SIRT1 was specifically deleted from the intestines of mice using the flox-Villin-Cre system (SIRT1 iKO mice). Intestinal and hepatic tissues were collected, and bile acid absorption was analyzed using the everted gut sac experiment. Systemic bile acid metabolism was studied in SIRT1 iKO and flox control mice placed on standard diets, diets containing 0.5% cholic acid or 1.25%

SUBMITTER: Kazgan N 

PROVIDER: S-EPMC4142427 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature