@article{JohannKleinertKlaus2021,
  author    = {Johann, Kornelia and Kleinert, Maximilian and Klaus, Susanne},
  title     = {The role of GDF15 as a myomitokine},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {11},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2073-4409},
  doi       = {10.3390/cells10112990},
  pages     = {16},
  year      = {2021},
  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.},
  language  = {en}
}
@article{OstIgualGilColemanetal.2020,
  author    = {Ost, Mario and Igual Gil, Carla and Coleman, Verena and Keipert, Susanne and Efstathiou, Sotirios and Vidic, Veronika and Weyers, Miriam and Klaus, Susanne},
  title     = {Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress},
  series = {EMBO reports},
  volume    = {21},
  journal   = {EMBO reports},
  number    = {3},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1469-221X},
  doi       = {10.15252/embr.201948804},
  pages     = {14},
  year      = {2020},
  abstract  = {Mitochondrial dysfunction promotes metabolic stress responses in a cell-autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1-TG) with compromised muscle-specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1-TG mice show a skeletal muscle-specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1-TG mice does not affect muscle wasting or transcriptional cell-autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress-induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15-dependent daytime-restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress-induced GDF15 in the regulation of systemic energy metabolism.},
  language  = {en}
}