Abstract
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.
Highlights
Growth differentiation factor 15 (GDF15) has been identified over 20 years ago as a cytokine in different patho-physiolgical contexts owing to the fact that it can be expressed and secreted by multiple tissues and cell types in response to cellular stress
Tahniosrfeixtsiaw-ciathchthexeiwa seylln-kdnrowmne, aictticoannsaolfsothaemheinlidorbartaeinobAePsiitny-tahsesoccoinatreodl mofonrabuidseitaieasn. dSovmome oitfinthge[s4e3d] ibsecsriedpeaintscireoslecoauslda codneptreonldceonntetrheofpfhoyosdioilnotgaikceal[4co4n].text and the duration and magnitude of the GDF15 signal, whichIthwasaismaplroeratadnyt tshheorwapneuintic20im07pltihcatioGnDsFfo15r aipnpjercotaiocnheisntamrgiceetinlegatdhsetGoDaFct1i5v–aGtiFoRnAoLf naexuirso. ns in hindbrain as well as in hypothalamic areas involved in appetite regulation such as the paraventricular nucleus of the hypothalamus (PVH) [24] but the nature of the Recent research on the GDF15–GFRAL axis has focused on its anorectic action and suggests that it acts as a mediator of the physiological responses to visceral malaise states such as the induction of food aversion, nausea, and emesis preceding the onset of anorexia, as shown in different rodent models and shrews [31,40,41,42]
The metabolic effects of GDF15 as an almost ubiquitously expressed cytokine have received considerable attention recently, much supported by the discovery of GFRAL as the specific receptor for GDF15, which is responsible for its central actions mainly related to appetite regulation
Summary
Growth differentiation factor 15 (GDF15) has been identified over 20 years ago as a cytokine in different patho-physiolgical contexts owing to the fact that it can be expressed and secreted by multiple tissues and cell types in response to cellular stress. In recent years has it been implicated as an important factor in the regulation of metabolic health and energy metabolism. Its role in appetite regulation has been emphasized since the discovery of the glial cell line-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as its hindbrain located receptor, which mediates the anorectic effects of GDF15. The general biology of GDF15 and its role in health and disease has been addressed in excellent and thorough recent reviews [1,2]. We will focus on the role of GDF15 as a mitokine, which is induced by mitochondrial stress and dysfunction as a possible mitohormesis mediator [3]. We will address the still controversial issue of GDF15 as a myomitokine [4] and its possible role in muscle-brain crosstalk
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
