Bile Acid Metabolites in Serum: Intraindividual Variation and Associations with Coronary Heart Disease, Metabolic Syndrome and Diabetes Mellitus

Abstract

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4,are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

“…We found large variations in fasting BA concentrations both within and between individuals, as depicted in Figure 1. This is in line with studies of non-bariatric subjects, which found large diurnal variations within individuals [41,42] and large variations in production and concentrations between individuals [43,44].…”

A Metabolomics-driven Elucidation of the Anti-obesity Mechanisms of Xanthohumol

“…Neither study reported bile acid measurements in plasma. However, the large diurnal and interindividual variation in plasma bile acid concentrations makes comparative measurements difficult (67). In agreement with this, targeted data mining of bile acids revealed great variation between XN-treated and control Zucker rats, and no significant changes were observed (data not shown).…”

Increased Bile Acid Synthesis and Deconjugation After Biliopancreatic Diversion

“…We find it unlikely that increased BA synthesis alone is sufficient to cause these effects, as we and others have found that BA synthesis also increases during conditions of metabolic impairment, including human obesity and T2D (26,36,37). On the other hand, it is possible that the interruption in enterohepatic circulation of BAs after BPD could play a part.…”