SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
13
11
2023
accepted:
01
08
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
12
8
2024
Statut:
epublish
Résumé
N-lactoyl-phenylalanine (Lac-Phe) is a lactate-derived metabolite that suppresses food intake and body weight. Little is known about the mechanisms that mediate Lac-Phe transport across cell membranes. Here we identify SLC17A1 and SLC17A3, two kidney-restricted plasma membrane-localized solute carriers, as physiologic urine Lac-Phe transporters. In cell culture, SLC17A1/3 exhibit high Lac-Phe efflux activity. In humans, levels of Lac-Phe in urine exhibit a strong genetic association with the SLC17A1-4 locus. Urine Lac-Phe levels are increased following a Wingate sprint test. In mice, genetic ablation of either SLC17A1 or SLC17A3 reduces urine Lac-Phe levels. Despite these differences, both knockout strains have normal blood Lac-Phe and body weights, demonstrating SLC17A1/3-dependent de-coupling of urine and plasma Lac-Phe pools. Together, these data establish SLC17A1/3 family members as the physiologic urine Lac-Phe transporters and uncover a biochemical pathway for the renal excretion of this signaling metabolite.
Identifiants
pubmed: 39134528
doi: 10.1038/s41467-024-51174-3
pii: 10.1038/s41467-024-51174-3
doi:
Substances chimiques
Lactates
0
Phenylalanine
47E5O17Y3R
N-lactoyl-phenylalanine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6895Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : DK124265
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : DK136526
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : P30DK116074
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : GM113854
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 431984000
Informations de copyright
© 2024. The Author(s).
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