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Updated: Apr 11, 2026

Ileectomy-induced Bile Overaccumulation in Mouse Intestine
Published on: August 21, 2017
Circadian control of bile acid synthesis by a KLF15-Fgf15 axis
Shuxin Han1, Sean Shuxin Han1, Rongli Zhang1
1Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, and Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
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.
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