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

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 [...