Page 93 - Human Bile Acid Metabolism: a Postprandial Perspective

Short term starvation and bile acid supplementation
[0.35] mmol/L vs. 40 h FAST: 4.2 [1.0] mmol/L; P < 0.05) but had no effect on premeal insulin concentrations (baseline 14 h FAST: 7.5 [15.0] pmol/L vs. 40 h FAST: 7.5 [0] pmol/L; P > 0.05). Extended fasting increased postprandial glucose and insulin concentrations (AUC0-240 glucose 14 h FAST: 1,401.0 [240.5] mmol/L × min vs. 40 h FAST: 1,579.5 [498.2] mmol/L × min; P < 0.05, 2-way RM-ANOVA. P < 0.01; post hoc analysis time (T) 60 P < 0.05 and T90 P < 0.01 AUC0-240 insulin 14 h FAST: 40,447.0 [8,775.0] pmol/L × min vs. 40 h FAST: 64,807.5 [67320.0] pmol/L × min; P < 0.01, 2-way RM-ANOVA P < 0.05, post hoc analysis T90, T120, and T180 P < 0.01) (Fig. 1, A and B), denoting that 40 h fasting induced glucose intolerance. iAUCs yielded the same results (data not shown).
Plasma BA concentrations after 40 h of fasting. Postprandial TBA concentrations
increased in both conditions (Fig. 1C). Fasting and postprandial BA levels showed
large interindividual variations in BA composition (Table 1). The 40-h fast did not 5 affect baseline (14 h FAST: 0.70 [0.63] μmol/L vs. 40 h FAST: 0.54 [0.60] μmol/L;
P > 0.05) or postprandial total BA levels in plasma (AUC0-240 14 h FAST: 989.3
[848.4] μmol/L × min vs. 40 h FAST: 987.5 [516.0] μmol/L × min; P > 0.05, 2-way
RM-ANOVA P > 0.05) (Table 1, Fig. 1C).
There was no significant effect of the 40-h fast on baseline levels or postprandial excursion of other individual BA species (Table 1). We did not find any differences in the fasted CA:CDCA ratio (14 h FAST 0.54 ± 0.3 vs. 40 h FAST 0.44 ± 0.1; P > 0.05) and the primary (CA and CDCA): secondary bile acid (DCA and UDCA) ratio (14 h FAST 1.52 ± 0.7 vs. 40 h FAST 1.31 ± 0.1; P > 0.05). Furthermore, the postprandial CA:CDCA ratio (AUC 14 h FAST 0.39 ± 0.2 vs. 40 h FAST 0.36 ± 0.1; P > 0.05) and the primary:secondary bile acid ratio (AUC 14 h FAST 2.6 ± 1.6 vs. 40 h FAST 2.6 ± 1.9; P > 0.05) did not differ.
Since we were interested in the correlations between plasma levels of BAs and insulin, we performed correlation analyses at different time points after ingestion of the meal. We observed a strong positive correlation between post absorptive insulin and gDCA levels at t = 60 min after an overnight fast (Spearman’s Rho 14 h FAST: r = +0.88, P < 0.01, Fig. 2A, 40 h FAST: r = +0.42, P = 0.27) and t = 90 min (14 h FAST: r = +0.75, P < 0.05; 40 h FAST: r = +0.73, P < 0.05). The correlation at 60 min was strongest after an overnight fast, where the correlation remained significant after correction for multiple testing. iAUCs showed no differences (data not shown).
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