Short-term and Divergent Regulation of FGF-19 and FGF-21 during Oral Lipid Tolerance Test but not Oral Glucose Tolerance Test

Abstract

Context: Regulation of FGF-19 and FGF-21 by oral uptake of lipids and carbohydrates in healthy individuals is poorly characterized.

Objective: We investigated the regulation of FGF-19 and FGF-21 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100).

Design and setting: 100 volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 h (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a special OLTT solution was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of FGF-19 and FGF-21 were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Mean FGF-19 levels ranged between 12 and 544 pg/ml with a fasting mean value of 105±81 pg/ml and 118±86 pg/ml in OLTT and OGTT. Mean FGF-21 levels ranged between 4 and 1 393 pg/ml with a fasting mean value of 160±204 pg/ml and 235±288 pg/ml in OLTT and OGTT. There was a significant, positive correlation between FGF-19 and FGF-21 in OLTT (p<0.001, r=0.5) and in OGTT (p=0.011, r=0.4). FGF-21 levels were positively correlated with waist circumference and waist hip-ratio in both cohorts. OGTT had no effect on FGF-19 and FGF-21. In contrast, FGF-19 levels were significantly induced and FGF-21 levels were significantly reduced during OLTT.

Conclusions: OLTT is a physiological inductor of FGF-19 and a repressor of FGF-21 in healthy adults. There is a significant and positive correlation between FGF-19 and FGF-21. Dietary lipids specifically and differentially regulate FGF-19 and FGF-21 whereas dietary carbohydrates have no effect. The present data provide the clinical basis for the postulated negative feedback loop between dietary lipids and postprandial inhibition of hepatic lipogenesis.

Key words

FGF-19 - FGF-21 - glucose tolerance test - lipid tolerance test

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