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Asynchronous rhythms of circulating conjugated and unconjugated bile acids in the modulation of human metabolism
Author(s) -
AlKhaifi A.,
Straniero S.,
Voronova V.,
Chernikova D.,
Sokolov V.,
Kumar C.,
Angelin B.,
Rudling M.
Publication year - 2018
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12811
Subject(s) - fgf19 , endocrinology , medicine , enterohepatic circulation , postprandial , cholestyramine , metabolism , cholesterol , insulin , chemistry , biology , fibroblast growth factor , receptor
Abstract Background and Objectives Bile acids ( BA s) traversing the enterohepatic circulation ( EHC ) influence important metabolic pathways. By determining individual serum BA s in relation to markers of metabolic activity, we explored how diurnal variations in their EHC relate to hepatic metabolism in normal humans. Methods Serum BA s, fibroblast growth factor 19 ( FGF 19), lipoproteins, glucose/insulin and markers of cholesterol and BA syntheses were monitored for 32 h in 8 healthy males. Studies were conducted at basal state and during initiation of cholestyramine treatment, with and without atorvastatin pretreatment. Time series cross‐correlation analysis, Bayesian structural model and Granger causality test were applied. Results Bile acids synthesis dominated daytime, and cholesterol production at night. Conjugated BA s peaked after food intake, with subsequent FGF 19 elevations. BA synthesis was reduced following conjugated BA and FGF 19 peaks. Cholestyramine reduced conjugated BA s and FGF 19, and increased BA and cholesterol production; the latter effects attenuated by atorvastatin. The relative importance of FGF 19 vs. conjugated BA s in this feedback inhibition could not be discriminated. Unconjugated BA s displayed one major peak late at night/early morning that was unrelated to FGF 19 and BA synthesis, and abolished by cholestyramine. The normal suppression of serum triglycerides, glucose and insulin observed at night was attenuated by cholestyramine. Conclusions Conjugated and unconjugated BA s have asynchronous rhythms of EHC in humans. Postprandial transintestinal flux of conjugated BA s increases circulating FGF 19 levels and suppresses BA synthesis. Unconjugated BA s peak late at night, indicating a non‐postprandial diurnal change in human gut microflora, the physiological implications of which warrants further study.