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

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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, bind 12, nr. 1, 1041, s. 1041. https://doi.org/10.1038/s41467-021-21309-x

APA

CBE

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. 12(1):1041. https://doi.org/10.1038/s41467-021-21309-x

MLA

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Author

Klein, Anders B ; Nicolaisen, Trine S ; Ørtenblad, Niels ; Gejl, Kasper D ; Jensen, Rasmus ; Fritzen, Andreas M ; Larsen, Emil L ; Karstoft, Kristian ; Poulsen, Henrik E ; Morville, Thomas ; Sahl, Ronni E ; Helge, Jørn W ; Lund, Jens ; Falk, Sarah ; Lyngbæk, Mark ; Ellingsgaard, Helga ; Pedersen, Bente K ; 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. I: Nature Communications. 2021 ; Bind 12, Nr. 1. s. 1041.

Bibtex

@article{8fdf4b53d7d84412b6729aa7ef41e64f,
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.",
keywords = "Adult, Animals, Appetite Regulation/physiology, Creatine Kinase/blood, Exercise/physiology, Feeding Behavior/physiology, Gene Expression Regulation, Glial Cell Line-Derived Neurotrophic Factor Receptors/deficiency, Growth Differentiation Factor 15/blood, Humans, Interleukin-10/blood, Interleukin-6/administration & dosage, Leptin/blood, Liver/drug effects, Male, Mice, Mice, Knockout, Motivation/physiology, Muscle, Skeletal/drug effects, Myocardium/metabolism, Physical Conditioning, Animal, Physical Endurance/physiology, Time Factors",
author = "Klein, {Anders B} and Nicolaisen, {Trine S} and Niels {\O}rtenblad and Gejl, {Kasper D} and Rasmus Jensen and Fritzen, {Andreas M} and Larsen, {Emil L} and Kristian Karstoft and Poulsen, {Henrik E} and Thomas Morville and Sahl, {Ronni E} and Helge, {J{\o}rn W} and Jens Lund and Sarah Falk and Mark Lyngb{\ae}k and Helga Ellingsgaard and Pedersen, {Bente K} 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",
year = "2021",
month = feb,
day = "15",
doi = "10.1038/s41467-021-21309-x",
language = "English",
volume = "12",
pages = "1041",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise

AU - Klein, Anders B

AU - Nicolaisen, Trine S

AU - Ørtenblad, Niels

AU - Gejl, Kasper D

AU - Jensen, Rasmus

AU - Fritzen, Andreas M

AU - Larsen, Emil L

AU - Karstoft, Kristian

AU - Poulsen, Henrik E

AU - Morville, Thomas

AU - Sahl, Ronni E

AU - Helge, Jørn W

AU - Lund, Jens

AU - Falk, Sarah

AU - Lyngbæk, Mark

AU - Ellingsgaard, Helga

AU - Pedersen, Bente K

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

PY - 2021/2/15

Y1 - 2021/2/15

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.

KW - Adult

KW - Animals

KW - Appetite Regulation/physiology

KW - Creatine Kinase/blood

KW - Exercise/physiology

KW - Feeding Behavior/physiology

KW - Gene Expression Regulation

KW - Glial Cell Line-Derived Neurotrophic Factor Receptors/deficiency

KW - Growth Differentiation Factor 15/blood

KW - Humans

KW - Interleukin-10/blood

KW - Interleukin-6/administration & dosage

KW - Leptin/blood

KW - Liver/drug effects

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Motivation/physiology

KW - Muscle, Skeletal/drug effects

KW - Myocardium/metabolism

KW - Physical Conditioning, Animal

KW - Physical Endurance/physiology

KW - Time Factors

UR - http://www.scopus.com/inward/record.url?scp=85101481595&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-21309-x

DO - 10.1038/s41467-021-21309-x

M3 - Journal article

C2 - 33589633

VL - 12

SP - 1041

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1041

ER -

ID: 62390053