Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat

Background: Elevated levels of circulating fibroblast growth factor 21 (FGF21) are commonly encountered in type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, all of which share exaggerated postprandial lipemia as a common proatherogenic feature. How FGF21 responds to an oral fat load in man is unknown. Methods: We measured liver fat contents and subcutaneous and visceral fat volumes in 47 healthy subjects, who also underwent an oral fat load with measurements of plasma FGF21 and free fatty acid (FFA). Triglyceride (TG), apolipoprotein B-48 (apoB-48), and apoB-100 concentrations were measured in triglyceride-rich lipoprotein (TRL) fractions. Results: When compared with fasting levels, the concentration of FGF21 decreased significantly at 4 h (P < 0.05) and tended to return to fasting levels at 8 h after an oral fat load. Fasting and postprandial FGF21 correlated significantly with liver fat as well as with TRLs in the chylomicron and especially in very low-density lipoprotein 1 (VLDL1) and VLDL2 fractions representing remnant particles, but not with FFA. Subjects with increased liver fat (>5%, n = 12) showed impaired suppression of FGF21 at 4 h (P < 0.05) and at 8 h (P = 0.01) and demonstrated higher postprandial TG area under the curve in plasma and TRL fractions (P <= 0.032) compared with those with normal liver fat (<= 5%, n = 35). Conclusions: We observed a significant decrease of FGF21 concentration after an oral fat load. Fasting and postprandial FGF21 levels were closely related to large VLDL and remnants, but not to plasma FFA. Our pilot findings suggest that the postprandial accumulation of TRL remnants and liver fat may modulate postprandial FGF21 levels.