title: Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Insulin and Incretin Biology, Hagedorn Research Institute, Novo Nordisk A/S, Gentofte, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Andersen
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D005215:Fasting / Q000097:blood* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors