title: Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis.
abstract: BACKGROUND
  Cold exposure stimulates fibroblast growth factor 21 (FGF21) secretion in animals, enhancing the cold-induced thermogenesis (CIT) response through browning of white adipose tissue. In humans, the effects of cold exposure on circulating FGF21 levels are unknown.
  
  
  OBJECTIVE
  Our objective was to evaluate the effects of mild cold exposure on circulating FGF21 and its relationship with CIT and lipolysis in humans.
  
  
  METHODS
  We conducted a randomized, single-blind, crossover intervention study at the National Institutes of Health Clinical Center.
  
  
  METHODS
  Participants were healthy adults.
  
  
  METHODS
  Subjects were exposed to a 12-h exposure to 24 or 19 C in a whole-room indirect calorimeter.
  
  
  METHODS
  Energy expenditure, plasma FGF 21, nonesterified fatty acid, and adipose tissue microdialysis glycerol concentrations were evaluated.
  
  
  RESULTS
  At 24 C, plasma FGF21 exhibited a diurnal rhythm, peaking at 0800 h [110 (59-178) pg/ml], and progressively dropped to a nadir at 1700 h [41 (21-71) pg/ml, P < 0.0001] before rising at 1900 h [60 (11-81) pg/ml, P < 0.0001]. Exposure at 19 C lessened the diurnal reduction of FGF21 observed at 24 C from 0800-1700 h and augmented overall FGF21 levels by 37 ± 45% (P = 0.01). The change in area under the curve plasma FGF21 between 19 and 24 C correlated positively with the change in area under the curve adipose microdialysate glycerol (R(2) = 0.35, P = 0.04) but not with nonesterified fatty acid. Cold-induced increase in FGF21 predicted greater rise in energy expenditure during cold exposure (β = 0.66, P = 0.027), independent of age, gender, fat mass, and lean mass.
  
  
  CONCLUSIONS
  Mild cold exposure increased circulating FGF21 levels, predicting greater lipolysis and CIT. A small reduction in environmental temperature is sufficient to modulate FGF21 diurnal rhythm in humans, which may mediate cold-induced metabolic changes similar to those in animals.
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Clinical Research Center, 10 Center Drive, Bethesda, Maryland 20892, USA. pcylee@gmail.com
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brychta
authors.forename: Joyce
authors.initials: J
authors.lastname: Linderman
authors.forename: Sheila
authors.initials: S
authors.lastname: Smith
authors.forename: Kong Y
authors.initials: KY
authors.lastname: Chen
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Celi
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D003080:Cold Temperature; D018592:Cross-Over Studies; D005260:Female; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D016037:Single-Blind Method; D022722:Thermogenesis / Q000502:physiology*; D055815:Young Adult
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors