Dataset Information

SLC17 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 also 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 SLC17-dependent de-coupling of urine and plasma Lac-Phe pools. Together, these data establish SLC17A1/3 family members as the physiologic urine transporters for Lac-Phe and uncover a biochemical pathway for the renal excretion of this signaling metabolite. Our data do not exclude the involvement of other transporters in mediating Lac-Phe transport.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: Veronica Li

LAB HEAD: Jonathan Zhong Long

PROVIDER: PXD054202 | Pride | 2024-10-17

REPOSITORIES: Pride

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			Action	DRS
	20230613_Long_VLi_13157_1_WT_1.raw	Raw
	20230613_Long_VLi_13157_1_WT_1.raw_20240715_Byonic.mgf	Mgf
	20230613_Long_VLi_13157_1_WT_1.raw_20240715_Byonic.mzid.gz	Mzid
	20230613_Long_VLi_13157_1_WT_1.raw_20240715_Byonic.xlsx	Xlsx
	20230613_Long_VLi_13157_2_WT1_2.raw	Raw

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

Li Veronica L VL Xiao Shuke S Schlosser Pascal P Scherer Nora N Wiggenhorn Amanda L AL Spaas Jan J Tung Alan Sheng-Hwa AS Karoly Edward D ED Köttgen Anna A Long Jonathan Z JZ

Nature communications 20240812 1

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 SLC ...[more]

PMID: 39134528

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