SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans.

Autor: Li VL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA., Xiao S; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA., Schlosser P; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.; Centre for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Freiburg, Germany., Scherer N; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany., Wiggenhorn AL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA., Spaas J; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA., Tung AS; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA., Karoly ED; Metabolon, Inc., Morrisville, NC, USA., Köttgen A; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.; Centre for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Freiburg, Germany., Long JZ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; The Phil & Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 12; Vol. 15 (1), pp. 6895. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1038/s41467-024-51174-3
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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