Body weight regulation via MT1-MMP-mediated cleavage of GFRAL.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
07
01
2021
accepted:
07
01
2022
pubmed:
19
2
2022
medline:
28
4
2022
entrez:
18
2
2022
Statut:
ppublish
Résumé
GDNF-family receptor a-like (GFRAL) has been identified as the cognate receptor of growth/differentiation factor 15 (GDF15/MIC-1), considered a key signaling axis in energy homeostasis and body weight regulation. Currently, little is known about the physiological regulation of the GDF15-GFRAL signaling pathway. Here we show that membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) is an endogenous negative regulator of GFRAL in the context of obesity. Overnutrition-induced obesity increased MT1-MMP activation, which proteolytically inactivated GFRAL to suppress GDF15-GFRAL signaling, thus modulating the anorectic effects of the GDF15-GFRAL axis in vivo. Genetic ablation of MT1-MMP specifically in GFRAL
Identifiants
pubmed: 35177851
doi: 10.1038/s42255-022-00529-5
pii: 10.1038/s42255-022-00529-5
doi:
Substances chimiques
Glial Cell Line-Derived Neurotrophic Factor Receptors
0
Matrix Metalloproteinase 14
EC 3.4.24.80
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
203-212Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM141089
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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