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

Abstract

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 (O5%, nZ12) showed impaired suppression of FGF21 at 4 h (P!0.05) and at 8 h (PZ0.01) 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%, nZ35). 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.

Serum TG-lowering properties of plant sterols and stanols are associated with decreased hepatic VLDL secretion

“…After administration of poloxamer 407, we observed a signifi cant decrease in VLDL-TG secretion in plasma in PSA-and PSE-fed mice Hepatic triglyceride levels have been described to determine for the number and size of VLDL-TG particles (28)(29)(30). However, in our study, hepatic triglyceride concentrations did not differ between the HFD-and PSE/ was examined ( 36 ).…”

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

“…Furthermore, one study reported on a decrease in postprandial FGF-21 concentration after oral fat load in healthy subjects and postulated that it was modulated by postprandial accumulation of triglyceride-rich lipoprotein fractions [17]. Another study examined changes in FGF-21 concentration, glucose, insulin and C-peptide levels after 75-g oral glucose tolerance test in healthy subjects, people with impaired glucose tolerance and patients with T2DM, respectively.…”

Fibroblast Growth Factor 21 is a Regulator of Energy Metabolism in the Liver and Adipose Tissue

“…Plasma concentrations and hepatic FGF21 mRNA expression increase during fasting and starvation, whereas in the fed state FGF-21 expression and plasma levels are low in rodents as well as in healthy human subjects [20,21]. The main stimuli that induce hepatic FGF-21 expression during fasting are free fatty acids (FFAs).…”

“…Ingestion of a mixed meal consisting of fat, carbohydrates, and protein suppresses FGF-21 concentrations 4-h postprandially in metabolically healthy subjects [21]. After an oral glucose tolerance test, the FGF-21 nadir is reached after 60 min and the fasting values, as well as the post-glucose decline, correlates inversely with glucose and insulin levels [64].…”

“…In addition, the postprandial decrease in FGF-21 is closely inversely related to postprandial intestinal and hepatic TG-rich lipoproteins and their degradation products termed remnant lipoproteins in healthy subjects. Surprisingly, postprandial plasma FFAs are not clearly related to FGF-21 concentration in humans [21], despite [29,47] Adaptation to ketosis + − [2,20] Adaptation to prolonged fasting + − [2,20] Hibernation + − [22] Adaptation to cold + (+) [49,66] Resistance to growth hormone + (+) [45,84] Food intake + (+) [83,86] +, Positive effects; −, negative effects. Less well characterized or controversial roles for FGF-21 in humans are shown in brackets.…”