Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Front Endocrinol (Lausanne). 2022 Dec 5;13:1037948. doi: 10.3389/fendo.2022.1037948. eCollection 2022.
Growth differentiation factor (GDF)-15 is implicated in regulation of metabolism and circulating GDF15 increases in response to exercise. The source and regulation of the exercise-induced increase in GDF15 is, however not known.
Plasma GDF15 was measured by ELISA under the following conditions: 1) Arterial-to-hepatic venous differences sampled before, during, and after exercise in healthy male subjects (n=10); 2) exogenous glucagon infusion compared to saline infusion in resting healthy subjects (n=10); 3) an acute exercise bout with and without a pancreatic clamp (n=6); 4) healthy subjects for 36 hours (n=17), and 5) patients with anorexia nervosa (n=25) were compared to healthy age-matched subjects (n=25). Tissue GDF15 mRNA content was determined in mice in response to exhaustive exercise (n=16).
The splanchnic bed released GDF15 to the circulation during exercise and increasing the glucagon-to-insulin ratio in resting humans led to a 2.7-fold (P<0.05) increase in circulating GDF15. Conversely, inhibiting the exercise-induced increase in the glucagon-to-insulin ratio blunted the exercise-induced increase in circulating GDF15. Fasting for 36 hours did not affect circulating GDF15, whereas resting patients with anorexia nervosa displayed elevated plasma concentrations (1.4-fold, P<0.05) compared to controls. In mice, exercise increased GDF15 mRNA contents in liver, muscle, and adipose tissue.
In humans, GDF15 is a "hepatokine" which increases during exercise and is at least in part regulated by the glucagon-to-insulin ratio. Moreover, chronic energy deprivation is associated with elevated plasma GDF15, which supports that GDF15 is implicated in metabolic signalling in humans.
生长分化因子 15（GDF-15）参与代谢的调节，循环中的 GDF15 会随着运动而增加。然而，运动诱导的 GDF15 增加的来源和调节机制尚不清楚。
通过酶联免疫吸附试验（ELISA）在以下条件下测量血浆 GDF15：1）健康男性受试者运动期间和运动前后的动脉-肝静脉差异（n=10）；2）在休息的健康受试者中比较外源性胰高血糖素输注与生理盐水输注（n=10）；3）有和没有胰腺钳夹的急性运动（n=6）；4）健康受试者持续 36 小时（n=17）；5）神经性厌食症患者（n=25）与健康年龄匹配的受试者（n=25）相比。还在运动后的小鼠中测定组织 GDF15 mRNA 含量（n=16）。
运动期间内脏床将 GDF15 释放到循环中，而在休息的人类中增加胰高血糖素与胰岛素的比值导致循环中 GDF15 增加 2.7 倍（P<0.05）。相反，抑制运动引起的胰高血糖素与胰岛素比值的增加会削弱运动引起的循环 GDF15 的增加。禁食 36 小时不会影响循环 GDF15，而休息的神经性厌食症患者的血浆浓度升高（1.4 倍，P<0.05）与对照组相比。在小鼠中，运动增加了肝脏、肌肉和脂肪组织中的 GDF15 mRNA 含量。
在人类中，GDF15 是一种“肝激素”，在运动期间增加，至少部分受到胰高血糖素与胰岛素比值的调节。此外，慢性能量剥夺与升高的血浆 GDF15 相关，这表明 GDF15 参与人类的代谢信号转导。
