Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers.

Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective of this study was to elucidate the 24-h profiling of plasma FGF21 during a 72-h fast. After an initial 12-h overnight fast, plasma levels of FGF21 together with circulating levels of glucose, insulin, glucagon and free fatty acids (FFA) were measured every 6 h during a 72-h fast in healthy female volunteers (n = 14). During the fast, plasma glucose and serum insulin gradually decreased whilst glucagon and FFA levels increased. Mean 24-h plasma FGF21 levels did not increase during the 72-h fast, but, despite large inter-individually variations, a significant circadian rhythm was observed. Thus, during the first day, plasma FGF21 increased from 125 pg/ml (16-142) at 8.30 a.m to peak levels of 224 pg/ml (88-326) at 2.30 a.m (P = 0·0215), the second day from 60 pg/ml (7-74) at 8.30 a.m to 268 pg/ml (103-410) at 2.30 a.m. (P = 0·0010) and the third day from 94 pg/ml (9-146) to 151 pg/ml (87-207) at 2.30 a.m. (P = 0·0049). Cortisol also showed circadian regulation and peaked at 8.30 a.m every day, 6 h after the observed FGF21 peak. Plasma FGF21 follows a circadian rhythm during a 72-h fast in healthy female subjects. The circadian regulation has a stronger impact on plasma FGF21 than the fasting status over 72-h period.