{"doi":"10.1038/s41467-024-51174-3","title":"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. The lactate metabolite N-lactoyl-phenylalanine (Lac-Phe) plays a role in suppressing food intake and body weight. Here, the authors identify kidney transporters responsible for the renal excretion of Lac-Phe. This discovery highlights a pathway for Lac-Phe regulation in mice and humans.","journal":"Nature Communications","year":2024,"id":428645,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1202658,"name":"Shuke Xiao","orcid":"0000-0003-2103-128X","position":1,"is_corresponding":false},{"id":334102,"name":"Pascal Schlosser","orcid":"0000-0002-8460-0462","position":2,"is_corresponding":false},{"id":896976,"name":"Nora Scherer","orcid":"0000-0001-7057-7663","position":3,"is_corresponding":false},{"id":840060,"name":"Amanda L. Wiggenhorn","orcid":"0000-0001-9413-690X","position":4,"is_corresponding":false},{"id":1204056,"name":"Jan Spaas","orcid":"0000-0002-4953-2505","position":5,"is_corresponding":false},{"id":840062,"name":"Alan Sheng-Hwa Tung","orcid":"0000-0002-0669-1928","position":6,"is_corresponding":false},{"id":373846,"name":"Edward D. Karoly","orcid":"0000-0003-3421-515X","position":7,"is_corresponding":false},{"id":49742,"name":"Anna Köttgen","orcid":"0000-0002-4671-3714","position":8,"is_corresponding":false},{"id":259637,"name":"Jonathan Z. Long","orcid":"0000-0003-2631-7463","position":9,"is_corresponding":false},{"id":259635,"name":"Veronica L. Li","orcid":"0000-0001-8888-3853","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T01:59:02.165535Z","pmid":"39134528","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}