Abstract
BackgroundDiurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis.Methods and ResultsThe current study depicted diurnal variations of individual BAs detected by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) in serum and livers collected from C57BL/6 mice fed a regular chow or a chow containing cholestyramine (resin). Circadian rhythms of mRNA of vital BA-related nuclear receptors, enzymes, and transporters in livers and ilea were determined in control- and resin-fed mice, as well as in farnesoid X receptor (FXR) null mice. The circadian profiles of BAs showed enhanced bacterial dehydroxylation during the fasting phase and efficient hepatic reconjugation of BAs in the fed phase. The resin removed more than 90% of BAs with β-hydroxy groups, such as muricholic acids and ursodeoxycholic acid, from serum and livers, but did not exert as significant influence on CA and CDCA in both compartments. Both resin-fed and FXR-null mouse models indicate that BAs regulate their own biosynthesis through the FXR-regulated ileal fibroblast growth factor 15. BA flux also influences the daily mRNA levels of multiple BA transporters.ConclusionBA concentration and composition exhibit circadian variations in mouse liver and serum, which influences the circadian rhythms of BA metabolizing genes in liver and ileum. The diurnal variations of BAs appear to serve as a signal that coordinates daily nutrient metabolism in mammals.
Highlights
Organisms have developed 24-hr rhythmic physiological processes to adapt to daily environmental changes
bile acid (BA) concentration and composition exhibit circadian variations in mouse liver and serum, which influences the circadian rhythms of BA metabolizing genes in liver and ileum
The diurnal variations of BAs appear to serve as a signal that coordinates daily nutrient metabolism in mammals
Summary
Organisms have developed 24-hr (circadian) rhythmic physiological processes to adapt to daily environmental changes. The main circadian clock is situated in the suprachiasmatic nucleus in the brain and synchronizes peripheral clocks. Peripheral tissues, like liver, can generate oscillations independent of the suprachiasmatic nucleus [1]. A special group of clock genes, organized in feedback loops, are responsible for the circadian rhythms in both the suprachiasmatic nucleus and peripheral organs. The phase of the suprachiasmatic nucleus neurons is mainly entrained by the light-dark cycle, whereas that of peripheral organs, like liver and intestine, is more influenced by the feeding-fasting cycles [2]. Clocks in peripheral tissues, such as lung, were shown to be sensitive to temperature changes within physiological range [3]. BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis
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