# Role of the renal organic anion transporter OAT1 in metabolism and physiology

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $547,010

## Abstract

PROJECT SUMMARY/ABSTRACT
Owing to new regulatory guidelines, the organic anion transporter (OAT1)--a transporter discovered by the PI's
group (as NKT) and which is involved in the elimination of many common drugs--has received considerable
attention. But nearly all the published studies continue to focus on common drugs rather than endogenous
substrates of the transporter, which is highly conserved from an evolutionary standpoint. Metabolomics
analysis of our Oat1 knockout mice (Oat1KO), as well as in vitro transport data, indicate that OAT1 is a
major transporter of metabolites, signaling molecules, vitamins, gut microbiome products, and
antioxidants. Our previous genome-scale metabolic reconstructions of altered metabolism of the Oat1KO
mouse under normal dietary conditions enabled us to create the first multispecific "drug" transporter (OAT1)-
centered metabolic network--which was further supported by considerable metabolomics and in vitro data.
Many pathways (e.g., fatty acids, gut microbiome products, branched chain amino acids) in this largely
validated network of ~150-200 metabolites are also known to be important in metabolic diseases such as
diabetes, metabolic syndrome, obesity, and gut microbiome-associated illness. In this proposal: 1) We will use
dietary modifications (e.g., high fat, branched chain amino acids) and antibiotic treatment of the Oat1 KO mice
to define the role of Oat1 under conditions applicable to metabolic diseases. We will test the binding of
metabolites revealed by metabolomics under the various dietary conditions (or disease models) using a high
throughput unlabeled (BLI) assay to quantify the interaction of metabolites with OAT1; this information will be
used to prioritize metabolites for subsequent uptake assays involving the use of radiolabeled compounds. 2)
We will then use this information, together with gene expression data from the knockout tissues under various
dietary conditions, to reconstruct a metabolic network for each of these dietary (pathological model) conditions-
-using methods we have previously successfully used to create an "OAT1-centered metabolic network" under
normal dietary conditions. Together, these studies will help define the unique roles of OAT1 in regulation
of aberrant metabolism in these dysregulated metabolic states. Finally, we discuss how this information will
set the stage for understanding aspects of drug-induced metabolic syndrome in patients taking OAT1-
transported drugs. We have proven expertise in the necessary techniques and a team of world-class
collaborators to ensure success.

## Key facts

- **NIH application ID:** 10179427
- **Project number:** 5R01GM132938-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SANJAY K NIGAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $547,010
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179427

## Citation

> US National Institutes of Health, RePORTER application 10179427, Role of the renal organic anion transporter OAT1 in metabolism and physiology (5R01GM132938-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10179427. Licensed CC0.

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