Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise.
Nat Commun
; 12(1): 1041, 2021 02 15.
Article
in En
| MEDLINE
| ID: mdl-33589633
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Appetite Regulation
/
Physical Endurance
/
Exercise
/
Glial Cell Line-Derived Neurotrophic Factor Receptors
/
Growth Differentiation Factor 15
/
Feeding Behavior
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Animals
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Document type:
Article
Affiliation country: