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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise. / Klein, Anders Bue; Nicolaisen, Trine Sand; Ørtenblad, Niels; Gejl, Kasper Degn; Jensen, Rasmus; Fritzen, Andreas Mæchel; Larsen, Emil L; Karstoft, Kristian; Poulsen, Henrik E; Morville, Thomas; Sahl, Ronni Eg; Helge, Jørn Wulff; Lund, Jens; Falk, Sarah; Lyngbæk, Mark; Ellingsgaard, Helga; Pedersen, Bente Klarlund; Lu, Wei; Finan, Brian; Jørgensen, Sebastian B; Seeley, Randy J; Kleinert, Maximilian; Kiens, Bente; Richter, Erik A.; Clemmensen, Christoffer.

In: Nature Communications, Vol. 12, 1041, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Klein, AB, Nicolaisen, TS, Ørtenblad, N, Gejl, KD, Jensen, R, Fritzen, AM, Larsen, EL, Karstoft, K, Poulsen, HE, Morville, T, Sahl, RE, Helge, JW, Lund, J, Falk, S, Lyngbæk, M, Ellingsgaard, H, Pedersen, BK, Lu, W, Finan, B, Jørgensen, SB, Seeley, RJ, Kleinert, M, Kiens, B, Richter, EA & Clemmensen, C 2021, 'Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise', Nature Communications, vol. 12, 1041. https://doi.org/10.1038/s41467-021-21309-x

APA

Klein, A. B., Nicolaisen, T. S., Ørtenblad, N., Gejl, K. D., Jensen, R., Fritzen, A. M., Larsen, E. L., Karstoft, K., Poulsen, H. E., Morville, T., Sahl, R. E., Helge, J. W., Lund, J., Falk, S., Lyngbæk, M., Ellingsgaard, H., Pedersen, B. K., Lu, W., Finan, B., ... Clemmensen, C. (2021). Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise. Nature Communications, 12, [1041]. https://doi.org/10.1038/s41467-021-21309-x

Vancouver

Klein AB, Nicolaisen TS, Ørtenblad N, Gejl KD, Jensen R, Fritzen AM et al. Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise. Nature Communications. 2021;12. 1041. https://doi.org/10.1038/s41467-021-21309-x

Author

Klein, Anders Bue ; Nicolaisen, Trine Sand ; Ørtenblad, Niels ; Gejl, Kasper Degn ; Jensen, Rasmus ; Fritzen, Andreas Mæchel ; Larsen, Emil L ; Karstoft, Kristian ; Poulsen, Henrik E ; Morville, Thomas ; Sahl, Ronni Eg ; Helge, Jørn Wulff ; Lund, Jens ; Falk, Sarah ; Lyngbæk, Mark ; Ellingsgaard, Helga ; Pedersen, Bente Klarlund ; Lu, Wei ; Finan, Brian ; Jørgensen, Sebastian B ; Seeley, Randy J ; Kleinert, Maximilian ; Kiens, Bente ; Richter, Erik A. ; Clemmensen, Christoffer. / Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise. In: Nature Communications. 2021 ; Vol. 12.

Bibtex

@article{ae58f7a64bbf4741ac834a5608702be2,
title = "Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise",
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.",
author = "Klein, {Anders Bue} and Nicolaisen, {Trine Sand} and Niels {\O}rtenblad and Gejl, {Kasper Degn} and Rasmus Jensen and Fritzen, {Andreas M{\ae}chel} and Larsen, {Emil L} and Kristian Karstoft and Poulsen, {Henrik E} and Thomas Morville and Sahl, {Ronni Eg} and Helge, {J{\o}rn Wulff} and Jens Lund and Sarah Falk and Mark Lyngb{\ae}k and Helga Ellingsgaard and Pedersen, {Bente Klarlund} and Wei Lu and Brian Finan and J{\o}rgensen, {Sebastian B} and Seeley, {Randy J} and Maximilian Kleinert and Bente Kiens and Richter, {Erik A.} and Christoffer Clemmensen",
note = "CURIS 2021 NEXS 073",
year = "2021",
doi = "10.1038/s41467-021-21309-x",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

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 -

ID: 256980162