Carbohydrate feeding dissociates the postprandial FGF19 response from circulating bile acid levels in humans.

CONTEXT Fibroblast growth factor 19 (FGF19) improves glycemic control in diabetic animals and is secreted from the gastrointestinal tract after meals in response to bile acid stimulation. OBJECTIVE We sought to understand how ingestion of carbohydrates, protein or lipids affect both FGF19 and bile acid concentrations in human plasma, with the hypothesis that variation in the bile acid response to different macronutrients would predict differences in plasma FGF19 levels. DESIGN This was a randomized, within-subjects crossover study. SETTING The study was conducted at a university clinical research center. PARTICIPANTS There were 16 healthy human subjects included in the study. INTERVENTIONS Isocaloric, isovolemic beverages composed primarily of carbohydrates, proteins, or lipids were provided to each participant on 3 separate occasions. MAIN OUTCOME MEASURES The magnitudes of postprandial rises of plasma FGF19 and total bile acid levels were determined. RESULTS All beverages induced an initial transient decline of plasma FGF19 levels during the first 60 minutes after consumption. For FGF19, the ingestion of carbohydrate was associated with the fastest and highest increase of plasma levels, returning to baseline at 5 hours. By comparison, the protein beverage induced a modest but significant elevation of FGF19 levels that peaked at the end of the 6-hour sampling interval, whereas a lipid beverage was without effect. In contrast, total bile acid levels increased in plasma only in response to a high-lipid beverage, demonstrating a marked divergence between the FGF19 and bile acid response to lipid vs carbohydrate. CONCLUSIONS A bile acid-independent mechanism is implicated in the effect of meals to raise plasma FGF19 concentrations.