Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise

Anders B. Klein, Trine S. Nicolaisen, Niels Ørtenblad, Kasper D. Gejl, Rasmus Jensen, Andreas M. Fritzen, Emil L. Larsen, Kristian Karstoft, Henrik E. Poulsen, Thomas Morville, Ronni E. Sahl, Jørn W. Helge, Jens Lund, Sarah Falk, Mark Lyngbæk, Helga Ellingsgaard, Bente K. Pedersen, Wei Lu, Brian Finan, Sebastian B. Jørgensen, Randy J. Seeley, Maximilian Kleinert, Bente Kiens, Erik A. Richter and Christoffer Clemmensen ()
Additional contact information
Anders B. Klein: University of Copenhagen
Trine S. Nicolaisen: University of Copenhagen
Niels Ørtenblad: University of Southern Denmark
Kasper D. Gejl: University of Southern Denmark
Rasmus Jensen: University of Southern Denmark
Andreas M. Fritzen: University of Copenhagen
Emil L. Larsen: University of Copenhagen
Kristian Karstoft: University of Copenhagen
Henrik E. Poulsen: University of Copenhagen
Thomas Morville: University of Copenhagen
Ronni E. Sahl: University of Copenhagen
Jørn W. Helge: University of Copenhagen
Jens Lund: University of Copenhagen
Sarah Falk: University of Copenhagen
Mark Lyngbæk: Rigshospitalet, University of Copenhagen
Helga Ellingsgaard: Rigshospitalet, University of Copenhagen
Bente K. Pedersen: Rigshospitalet, University of Copenhagen
Wei Lu: Novo Nordisk Research Center Indianapolis
Brian Finan: Novo Nordisk Research Center Indianapolis
Sebastian B. Jørgensen: Global Obesity and LD Research, Novo Nordisk A/S
Randy J. Seeley: University of Michigan
Maximilian Kleinert: University of Copenhagen
Bente Kiens: University of Copenhagen
Erik A. Richter: University of Copenhagen
Christoffer Clemmensen: University of Copenhagen

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21309-x

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DOI: 10.1038/s41467-021-21309-x

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