ArticleThe Journal of biological chemistry
A key role for the transporter OAT1 in systemic lipid metabolism.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- A Kidney-Microbiome Short- and Medium-Chain Fatty Acid Loop Mediated by OAT1: Implications for the Remote Sensing and Signaling Theory.International journal of molecular sciences · 2026Article
- Article
- Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule.Nature communications · 2026Article
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 2025Review
- The SGLT2 inhibitor dapagliflozin ameliorates renal fibrosis in hyperuricemic nephropathy.Cell reports. Medicine · 2024Article
- In Vivo Regulation of Small Molecule Natural Products, Antioxidants, and Nutrients by OAT1 and OAT3.Nutrients · 2024Article
- Remote effects of kidney drug transporter OAT1 on gut microbiome composition and urate homeostasis.JCI insight · 2023Article
- Review
- Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
- Regulation of Human Endogenous Metabolites by Drug Transporters and Drug Metabolizing Enzymes: An Analysis of Targeted SNP-Metabolite Associations.Metabolites · 2023Article
- The kidney drug transporter OAT1 regulates gut microbiome-dependent host metabolism.JCI insight · 2023Article
- Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions.Scientific reports · 2022Article
- AHR is a master regulator of diverse pathways in endogenous metabolism.Scientific reports · 2022Article
- Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma.Cancers · 2022Article
- Blockade of Organic Anion Transport in Humans After Treatment With the Drug Probenecid Leads to Major Metabolic Alterations in Plasma and Urine.Clinical pharmacology and therapeutics · 2022Article
- Metabolic mechanisms of acute proximal tubular injury.Pflugers Archiv : European journal of physiology · 2022Review
- SLC22 Transporters in the Fly Renal System Regulate Response to Oxidative Stress In Vivo.International journal of molecular sciences · 2021Article
- Molecular Properties of Drugs Handled by Kidney OATs and Liver OATPs Revealed by Chemoinformatics and Machine Learning: Implications for Kidney and Liver Disease.Pharmaceutics · 2021Article
- Coordinate regulation of systemic and kidney tryptophan metabolism by the drug transporters OAT1 and OAT3.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Organic anion transporter 1 (OAT1/SLC22A6) is a drug transporter with numerous xenobiotic and endogenous substrates. The Remote Sensing and Signaling Theory suggests that drug transporters with compatible ligand preferences can play a role in "organ crosstalk," mediating overall organismal communication. Other drug transporters are well known to transport lipids, but surprisingly little is known about the role of OAT1 in lipid metabolism. To explore this subject, we constructed a genome-scale metabolic model using omics data from the Oat1 knockout mouse. The model implicated OAT1 in the regulation of many classes of lipids, including fatty acids, bile acids, and prostaglandins. Accordingly, serum metabolomics of Oat1 knockout mice revealed increased polyunsaturated fatty acids, diacylglycerols, and long-chain fatty acids and decreased ceramides and bile acids when compared with wildtype controls. Some aged knockout mice also displayed increased lipid droplets in the liver when compared with wildtype mice. Chemoinformatics and machine learning analyses of these altered lipids defined molecular properties that form the structural basis for lipid-transporter interactions, including the number of rings, positive charge/volume, and complexity of the lipids. Finally, we obtained targeted serum metabolomics data after short-term treatment of rodents with the OAT-inhibiting drug probenecid to identify potential drug-metabolite interactions. The treatment resulted in alterations in eicosanoids and fatty acids, further supporting our metabolic reconstruction predictions. Consistent with the Remote Sensing and Signaling Theory, the data support a role of OAT1 in systemic lipid metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.