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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.* ; Jørgensen, S.B.* ; Seeley, R.J.* ; Kleinert, M. ; Kiens, B.* ; Richter, E.A.* ; Clemmensen, C.*

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

Nat. Commun. 12:1041 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Muscle Glycogen; Receptor; Increases; Biomarker; Level
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 1041 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Grants NIDDK NIH HHS