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

• Published in: American journal of physiology: endocrinology and metabolism 2019-09, Vol.317 (3), p.E494-E502
• Main Authors: van Nierop, F Samuel, Meessen, Emma C E, Nelissen, Kyra G M, Achterbergh, Roos, Lammers, Laureen A, Vaz, Frédéric M, Mathôt, Ron A A, Klümpen, Heinz-Josef, Olde Damink, Steven W, Schaap, Frank G, Romijn, Johannes A, Kemper, E Marleen, Soeters, Maarten R
• Format: Article
• Language: English
• Subjects: Acids; Bile; Bile acids; Bile Acids and Salts - blood; Bile Acids and Salts - pharmacology; Blood Glucose; Cross-Over Studies; Deoxycholic acid; Deoxycholic Acid - pharmacology; Dietary Supplements; Energy expenditure; Energy Metabolism; Experiments; Fasting; Fasting - physiology; Fibroblast growth factors; Fibroblast Growth Factors - biosynthesis; Fibroblast Growth Factors - blood; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - biosynthesis; Glucagon-Like Peptide 1 - blood; Glucose; Glycine; Growth factors; Human behavior; Humans; Insulin; Insulin - blood; Insulin Resistance; Laboratory testing; Male; Metabolism; Postprandial Period; Supplements; Young Adult
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/AJPENDO.00534.2018

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 : we tested 4-h mixed meal after an overnight fast and a 40-h fast. In , 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 , 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 , 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.