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.
J Clin Endocrinol Metab. 2013 Jan;98(1):E98-102. doi: 10.1210/jc.2012-3107. Epub 2012 Nov 12.
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.
Our objective was to evaluate the effects of mild cold exposure on circulating FGF21 and its relationship with CIT and lipolysis in humans.
We conducted a randomized, single-blind, crossover intervention study at the National Institutes of Health Clinical Center.
Participants were healthy adults.
Subjects were exposed to a 12-h exposure to 24 or 19 C in a whole-room indirect calorimeter.
Energy expenditure, plasma FGF 21, nonesterified fatty acid, and adipose tissue microdialysis glycerol concentrations were evaluated.
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.
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.
寒冷刺激会促使动物的成纤维细胞生长因子 21（FGF21）分泌，通过白色脂肪组织的褐变增强寒冷诱导的产热（CIT）反应。在人类中，寒冷暴露对循环 FGF21 水平的影响尚不清楚。
我们的目的是评估轻度寒冷暴露对循环 FGF21 的影响及其与人类 CIT 和脂肪分解的关系。
我们在国立卫生研究院临床中心进行了一项随机、单盲、交叉干预研究。
参与者为健康成年人。
受试者在整个房间间接热量计中暴露于 12 小时的 24 或 19°C 环境中。
评估能量消耗、血浆 FGF21、非酯化脂肪酸和脂肪组织微透析甘油浓度。
在 24°C 时，血浆 FGF21 呈昼夜节律，峰值出现在 0800 小时[110（59-178）pg/ml]，并逐渐下降至 1700 小时的最低点[41（21-71）pg/ml，P <0.0001]，然后在 1900 小时上升[60（11-81）pg/ml，P <0.0001]。在 19°C 下暴露会减少在 24°C 时观察到的 FGF21 昼夜下降，从 0800-1700 小时减少 37±45%（P=0.01）。19-24°C 之间的曲线下血浆 FGF21 面积变化与曲线下脂肪微透析液甘油面积变化呈正相关（R²=0.35，P=0.04），但与非酯化脂肪酸无关。FGF21 在寒冷刺激下的增加预测了寒冷暴露期间能量消耗的更大增加（β=0.66，P=0.027），独立于年龄、性别、脂肪量和瘦体量。
轻度寒冷暴露会增加循环 FGF21 水平，预测更大的脂肪分解和 CIT。环境温度的微小降低足以调节人类的 FGF21 昼夜节律，这可能介导与动物相似的寒冷诱导代谢变化。
