SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans
Abstract: 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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature Communications. - 15, 1 (2024) , 6895, ISSN: 2041-1723
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2024
- Urheber
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Li, Veronica L.
Xiao, Shuke
Schlosser, Pascal
Scherer, Nora
Wiggenhorn, Amanda L.
Spaas, Jan
Tung, Alan Sheng-Hwa
Karoly, Edward D.
Köttgen, Anna
Long, Jonathan Z.
- DOI
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10.1038/s41467-024-51174-3
- URN
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urn:nbn:de:bsz:25-freidok-2565864
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:37 MESZ
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Beteiligte
- Li, Veronica L.
- Xiao, Shuke
- Schlosser, Pascal
- Scherer, Nora
- Wiggenhorn, Amanda L.
- Spaas, Jan
- Tung, Alan Sheng-Hwa
- Karoly, Edward D.
- Köttgen, Anna
- Long, Jonathan Z.
- Universität
Entstanden
- 2024
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