title: Circadian rhythm of circulating fibroblast growth factor 21 is related to diurnal changes in fatty acids in humans.
abstract: BACKGROUND
  Fibroblast growth factor (FGF) 21 is an endocrine factor actively involved in glucose and lipid metabolism in rodents. However, little is known about its physiological function and regulation in humans. This study investigated the diurnal changes in circulating FGF21 concentrations and their association with other metabolic markers in both obese and lean individuals.
  
  
  METHODS
  A total of 36 volunteers were assigned to 2 groups. One group received 3 standardized meals and another group was fasted for 24 h. Blood samples were drawn every 30 min throughout a 24-h period. Circulating FGF21 concentrations were measured with an in-house chemiluminescence immunoassay. The effects of fatty acids on hepatic production of FGF21 were determined by using real-time PCR.
  
  
  RESULTS
  In both the fasting and standardized meals groups, circulating FGF21 began to rise at midnight, reaching a peak in the early morning and then declining to basal concentrations early in the afternoon. Baseline concentrations of circulating FGF21 were much higher in obese individuals than in lean individuals (P < 0.05). However, the magnitude of the nocturnal rise in circulating FGF21 was significantly blunted in obese individuals. The 24-h oscillatory pattern of circulating FGF21 resembled that of free fatty acids and cortisol, but was opposite to the patterns of insulin and glucose. Unsaturated fatty acids induced time-dependent expression of FGF21 mRNA in human hepatocytes.
  
  
  CONCLUSIONS
  These findings support the role of FGF21 as an important metabolic regulator that integrates the circadian rhythm with energy homeostasis in humans. Diurnal rhythms of circulating FGF21 could be partly caused by the oscillation of free fatty acids.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
authors.forename: Haoyong
authors.initials: H
authors.lastname: Yu
authors.forename: Fuzhen
authors.initials: F
authors.lastname: Xia
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Jialiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Gu
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhou
authors.forename: Junxi
authors.initials: J
authors.lastname: Lu
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm; D015331:Cohort Studies; D004435:Eating; D005215:Fasting; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007118:Immunoassay; D007328:Insulin / Q000097:blood; D008163:Luminescent Measurements; D008297:Male; D009765:Obesity / Q000097:blood; D012680:Sensitivity and Specificity
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D006854:Hydrocortisone