Circadian control of bile acid synthesis by a KLF15-Fgf15 axis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26040986.
- Also identified by DOI 10.1038/ncomms8231 and PMC identifier 4457302.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Circadian control of nutrient availability is critical to efficiently meet the energetic demands of an organism. Production of bile acids (BAs), which facilitate digestion and absorption of nutrients, is a major regulator of this process. Here we identify a KLF15-Fgf15 signalling axis that regulates circadian BA production. Systemic Klf15 deficiency disrupted circadian expression of key BA synthetic enzymes, tissue BA levels and triglyceride/cholesterol absorption. Studies in liver-specific Klf15-knockout mice suggested a non-hepatic basis for regulation of BA production. Ileal Fgf15 is a potent inhibitor of BA synthesis. Using a combination of biochemical, molecular and functional assays (including ileectomy and bile duct catheterization), we identify KLF15 as the first endogenous negative regulator of circadian Fgf15 expression. Elucidation of this novel pathway controlling circadian BA production has important implications for physiologic control of nutrient availability and metabolic homeostasis.
Medical subject headings
- Bile Acids and Salts
- Circadian Rhythm
- DNA-Binding Proteins
- Fibroblast Growth Factors
- Hepatocytes
- Ileum
- Liver
- RNA, Messenger
- Transcription Factors