TY - JOUR
T1 - Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise
AU - Klein, Anders Bue
AU - Nicolaisen, Trine Sand
AU - Ørtenblad, Niels
AU - Gejl, Kasper Degn
AU - Jensen, Rasmus
AU - Fritzen, Andreas Mæchel
AU - Larsen, Emil L
AU - Karstoft, Kristian
AU - Poulsen, Henrik E
AU - Morville, Thomas
AU - Sahl, Ronni Eg
AU - Helge, Jørn Wulff
AU - Lund, Jens
AU - Falk, Sarah
AU - Lyngbæk, Mark
AU - Ellingsgaard, Helga
AU - Pedersen, Bente Klarlund
AU - Lu, Wei
AU - Finan, Brian
AU - Jørgensen, Sebastian B
AU - Seeley, Randy J
AU - Kleinert, Maximilian
AU - Kiens, Bente
AU - Richter, Erik A.
AU - Clemmensen, Christoffer
N1 - CURIS 2021 NEXS 073
PY - 2021
Y1 - 2021
N2 - Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.
AB - Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.
U2 - 10.1038/s41467-021-21309-x
DO - 10.1038/s41467-021-21309-x
M3 - Journal article
C2 - 33589633
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1041
ER -