Asynchronous rhythms of circulating conjugated and unconjugated bile acids in the modulation of human metabolism

Abstract

Conjugated and unconjugated BAs have asynchronous rhythms of EHC in humans. Postprandial transintestinal flux of conjugated BAs increases circulating FGF19 levels and suppresses BA synthesis. Unconjugated BAs peak late at night, indicating a non-postprandial diurnal change in human gut microflora, the physiological implications of which warrants further study.

Model‐based data analysis of individual human postprandial plasma bile acid responses indicates a major role for the gallbladder and intestine

“…Therefore, the variability of the postprandial unconjugated bile acids response follows a different pattern compared to the other described bile acids (Figure f,j). The altered pattern of the unconjugated bile acids support the previous published asynchronous variations of unconjugated and conjugated bile acids (Al‐Khaifi et al, ).…”

“…Interestingly, these studies have highlighted an association between high postprandial glycemic variability and cardiometabolic risk (Hall et al, 2018;Jung, 2015), emphasizing the relevance of postprandial variability for metabolic health and thus the need for better quantification and analysis of postprandial variability (Rozendaal et al, 2018). High interindividual variability of postprandial bile concentrations is reported in the literature (Al-Khaifi et al, 2018;Eggink et al, 2017;Fiamoncini et al, 2017;Sonne et al, 2016;Steiner et al, 2011). Sonne et al investigated the postprandial response to four different liquid meals in patients with T2DM and controls and showed the wide variety of bile acid dynamics (Sonne et al, 2016).…”

“…The postprandial increase in bile acid concentrations as a result of gallbladder emptying is a potential metabolic signal within the enterohepatic cycle (Kuipers et al, 2014). Plasma bile acid concentrations consistently increase after a mixed meal test (MMT), but the timing, shape, and bile acid composition of the postprandial curve shows high variability between subjects (interindividual variability) (Al-Khaifi et al, 2018;Eggink et al, 2017;Gälman, Angelin, & Rudling, 2005;LaRusso, Korman, Hoffman, & Hofmann, 1974;Sonne et al, 2016;Steiner et al, 2011). It is unclear what underlies postprandial bile acid variability, as in silico analysis has demonstrated various factors influence postprandial response of bile acids (Sips et al, 2018).…”

Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism

“…Compared to humans, the basal turnover of BAs and cholesterol, as well as that of circulating LDL, is higher and the concentration of LDL cholesterol much lower in mice (5,6). On the other hand, interruption of the enterohepatic circulation of BAs seems to elicit stronger effects on cholesterol metabolism and LDL levels in humans (7). Partly based on their different hydrophobicity, individual BAs have varying influences on biliary lipid secretion, intestinal fat absorption and feedback inhibition of BA synthesis, the latter thought to occur predominantly through their interaction with the farnesoid X receptor (FXR) in the distal ileum and in the liver (6).…”

“…Lipoprotein profiles were obtained using fast performance liquid chromatography (FPLC) as described (27). Markers for BA production (7alpha-hydroxy-4-cholesten-3-one, C4), cholesterol synthesis (lathosterol), and cholesterol absorption (sitosterol and campesterol) were analyzed as described (7,28,29) BAs in serum and bile were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) using deuteriumlabeled standards of unconjugated and taurine conjugated BAs as described (7). Deuteriumlabelled standards of unconjugated, glycineand taurine-conjugated BAs were from Steraloids, Inc. (Newport, RI, USA).…”