Mild Cold Exposure Modulates Fibroblast Growth Factor 21 (FGF21) Diurnal Rhythm in Humans: Relationship between FGF21 Levels, Lipolysis, and Cold-Induced Thermogenesis

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 1; pp. E98 - E102
• Main Authors: Lee, Paul, Brychta, Robert J., Linderman, Joyce, Smith, Sheila, Chen, Kong Y., Celi, Francesco S.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2013; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adipose tissue; Adult; Body fat; Circadian Rhythm - physiology; Cold; Cold Temperature; Cross-Over Studies; Diurnal; Energy expenditure; Fatty acids; Female; Fibroblast Growth Factors - analysis; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - metabolism; Fibroblasts; Glycerol; Growth factors; Humans; JCEM Online: Brief Reports; Lipolysis; Lipolysis - physiology; Male; Microdialysis; Middle Aged; Osmolar Concentration; Single-Blind Method; Thermogenesis; Thermogenesis - physiology; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-3107

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.