Differential effects of a 40-hour fast and bile acid supplementation on human GLP-1 and FGF19 responses

Bile acids, glucagon-like peptide-1 (GLP-1), and fibroblast growth factor 19 (FGF19) play an important role in postprandial metabolism. In this study, we investigated the postprandial bile acid response in plasma and its relation to insulin, GLP-1, and FGF19. First, we investigated the postprandial response to 40-h fast. Then we administered glycine-conjugated deoxycholic acid (gDCA) with the meal. We performed two separate observational randomized crossover studies on healthy, lean men. In experiment 1: we tested 4-h mixed meal after an overnight fast and a 40-h fast. In experiment 2, we tested a 4-h mixed meal test with and without gDCA supplementation. Both studies measured postprandial glucose, insulin, bile acids, GLP-1, and FGF19. In experiment 1, 40 h of fasting induced insulin resistance and increased postprandial GLP-1 and FGF19 concentrations. After an overnight fast, we observed strong correlations between postprandial insulin and gDCA levels at specific time points. In experiment 2, administration of gDCA increased GLP-1 levels and lowered late postprandial glucose without effect on FGF19. Energy expenditure was not affected by gDCA administration. Unexpectedly, 40 h of fasting increased both GLP-1 and FGF19, where the former appeared bile acid independent and the latter bile acid dependent. Second, a single dose of gDCA increased postprandial GLP-1. Therefore, our data add complexity to the physiological regulation of the enterokines GLP-1 and FGF19 by bile acids.