Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants.

ABSTRACT: Diet1 modulates intestinal production of the hormone, fibroblast growth factor (FGF)15, which signals in liver to regulate bile acid synthesis. C57BL/6ByJ mice with a spontaneous Diet1-null mutation are resistant to hypercholesterolemia compared with wild-type C57BL/6J mice through enhanced cholesterol conversion to bile acids. To further characterize the role of Diet1 in metabolism, we generated Diet1^-/- mice on the C57BL/6J genetic background. C57BL/6J Diet1^-/- mice had elevated bile acid levels, reduced Fgf15 expression, and increased gastrointestinal motility and intestinal luminal water content, which are symptoms of bile acid diarrhea (BAD) in humans. Natural genetic variation in Diet1 mRNA expression levels across 76 inbred mo

SUBMITTER: Lee JM 

PROVIDER: S-EPMC5832924 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature