Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced …

P Lee, RJ Brychta, J Linderman, S Smith… - The Journal of …, 2013 - academic.oup.com
P Lee, RJ Brychta, J Linderman, S Smith, KY Chen, FS Celi
The Journal of Clinical Endocrinology & Metabolism, 2013academic.oup.com
Context: 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. Design and Setting:
We conducted a randomized, single-blind, crossover intervention study at the National …
Context
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.
Design and Setting
We conducted a randomized, single-blind, crossover intervention study at the National Institutes of Health Clinical Center.
Participants
Participants were healthy adults.
Intervention
Subjects were exposed to a 12-h exposure to 24 or 19 C in a whole-room indirect calorimeter.
Outcome Measures
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 (R2 = 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.
Oxford University Press