Cold exposure modulates potential brown adipokines in humans, but only FGF21 is associated with brown adipose tissue volume

Objective: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans.Methods: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 +/- 2.3 y; 24.9 +/- 5.1 kg/m(2)). BAT volume, F-18-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure.Results: Cold exposure increased the concentration of CXCL14 (Delta 2h = 0.58 +/- 0.98 ng/mL; p = 0.007), GDF15 (Delta 2h = 19.63 +/- 46.2 pg/mL; p = 0.013), FGF21 (Delta 2h = 33.72 +/- 55.13 pg/mL; p = 0.003), and IL6 (Delta 1h = 1.98 +/- 3.56 pg/mL; p = 0.048) and reduced BMP8b (Delta 2h = -37.12 +/- 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Delta 2h: beta = 0.456; R-2 = 0.307; p = 0.001), but not with F-18-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity.Conclusions: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.