Group of Muscle Physiology and Metabolism, German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany.
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark.
Cells. 2021 Nov 3;10(11):2990. doi: 10.3390/cells10112990.
Growth differentiation factor 15 (GDF15) is a cytokine best known for affecting systemic energy metabolism through its anorectic action. GDF15 expression and secretion from various organs and tissues is induced in different physiological and pathophysiological states, often linked to mitochondrial stress, leading to highly variable circulating GDF15 levels. In skeletal muscle and the heart, the basal expression of GDF15 is very low compared to other organs, but GDF15 expression and secretion can be induced in various stress conditions, such as intense exercise and acute myocardial infarction, respectively. GDF15 is thus considered as a myokine and cardiokine. GFRAL, the exclusive receptor for GDF15, is expressed in hindbrain neurons and activation of the GDF15-GFRAL pathway is linked to an increased sympathetic outflow and possibly an activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. There is also evidence for peripheral, direct effects of GDF15 on adipose tissue lipolysis and possible autocrine cardiac effects. Metabolic and behavioral outcomes of GDF15 signaling can be beneficial or detrimental, likely depending on the magnitude and duration of the GDF15 signal. This is especially apparent for GDF15 production in muscle, which can be induced both by exercise and by muscle disease states such as sarcopenia and mitochondrial myopathy.
生长分化因子 15（GDF15）是一种细胞因子，以其厌食作用影响全身能量代谢而闻名。在不同的生理和病理状态下，各种器官和组织都会诱导 GDF15 的表达和分泌，这通常与线粒体应激有关，导致循环 GDF15 水平高度变化。在骨骼肌和心脏中，与其他器官相比，GDF15 的基础表达水平非常低，但在各种应激条件下，如剧烈运动和急性心肌梗死，GDF15 的表达和分泌可以被诱导。因此，GDF15 被认为是一种肌因子和心因子。GDF15 的唯一受体 GFRAL 在后脑神经元中表达，GDF15-GFRAL 途径的激活与交感神经输出增加有关，可能与下丘脑-垂体-肾上腺（HPA）应激轴的激活有关。也有证据表明 GDF15 对脂肪组织脂肪分解有外周、直接的作用，并且可能对心脏有自分泌作用。GDF15 信号的代谢和行为结果可能是有益的，也可能是有害的，这可能取决于 GDF15 信号的幅度和持续时间。对于肌肉中 GDF15 的产生尤其如此，运动和肌肉疾病状态（如肌肉减少症和线粒体肌病）都可以诱导 GDF15 的产生。
