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Tytuł pozycji:

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

Tytuł:
Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise.
Autorzy:
Klein AB; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nicolaisen TS; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Ørtenblad N; Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
Gejl KD; Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
Jensen R; Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
Fritzen AM; Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Larsen EL; Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
Karstoft K; Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.; Centre of Inflammation and Metabolism, Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Poulsen HE; Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
Morville T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Sahl RE; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Helge JW; Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Lund J; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Falk S; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Lyngbæk M; Centre of Inflammation and Metabolism, Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Ellingsgaard H; Centre of Inflammation and Metabolism, Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Pedersen BK; Centre of Inflammation and Metabolism, Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Lu W; Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA.
Finan B; Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA.
Jørgensen SB; Global Obesity and LD Research, Novo Nordisk A/S, Maaloev, Denmark.
Seeley RJ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Kleinert M; Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.; Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Kiens B; Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Richter EA; Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Clemmensen C; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. .
Źródło:
Nature communications [Nat Commun] 2021 Feb 15; Vol. 12 (1), pp. 1041. Date of Electronic Publication: 2021 Feb 15.
Typ publikacji:
Journal Article; Observational Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [London] : Nature Pub. Group
MeSH Terms:
Appetite Regulation/*physiology
Exercise/*physiology
Feeding Behavior/*physiology
Glial Cell Line-Derived Neurotrophic Factor Receptors/*genetics
Growth Differentiation Factor 15/*genetics
Physical Endurance/*physiology
Adult ; Animals ; Creatine Kinase/blood ; Creatine Kinase/genetics ; Gene Expression Regulation ; Glial Cell Line-Derived Neurotrophic Factor Receptors/deficiency ; Growth Differentiation Factor 15/blood ; Growth Differentiation Factor 15/metabolism ; Humans ; Interleukin-10/blood ; Interleukin-10/genetics ; Interleukin-6/administration & dosage ; Leptin/blood ; Leptin/genetics ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Mice, Knockout ; Motivation/physiology ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; Physical Conditioning, Animal ; Time Factors
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Grant Information:
P30 DK020572 United States DK NIDDK NIH HHS; P30 DK089503 United States DK NIDDK NIH HHS; R01 DK119188 United States DK NIDDK NIH HHS
Substance Nomenclature:
0 (GDF15 protein, human)
0 (Gdf15 protein, mouse)
0 (Glial Cell Line-Derived Neurotrophic Factor Receptors)
0 (Growth Differentiation Factor 15)
0 (IL10 protein, human)
0 (IL6 protein, human)
0 (Interleukin-6)
0 (LEP protein, human)
0 (Leptin)
130068-27-8 (Interleukin-10)
EC 2.7.3.2 (Creatine Kinase)
Entry Date(s):
Date Created: 20210216 Date Completed: 20210223 Latest Revision: 20210723
Update Code:
20240104
PubMed Central ID:
PMC7884842
DOI:
10.1038/s41467-021-21309-x
PMID:
33589633
Czasopismo naukowe
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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