# Quantifying Enteric Metabolism of Branched-chain Amino Acids in Relation to Other Dietary and Microbiota Nutrients

> **NIH NIH R00** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2024 · $249,000

## Abstract

Project Summary/Abstract
Research: Pharmaceuticals modifying intestinal incretin secretion and gluconeogenesis are promising new
therapies for obesity and diabetes mellitus, but their mechanisms of action are poorly understood limiting their
application. Elevated circulating pools of the essential branched-chain amino acids (BCAAs) and their
metabolites are consistently associated with obesity and diabetes with research primarily focused on liver and
muscle metabolism of dietary protein without considering intestine amino acid metabolism. Circulating BCAAs
in mammals must either originate from the diet or the microbiota residing in the lumen that upregulates its
expression of BCAA enzymes in obese and insulin-resistant animal models. The amino acid glutamine provides
significant energy to the intestine in fasted and fed states, reducing glucose oxidation by intestine cells but it is
not known if BCAAs drive similar metabolic changes. The intestine also metabolizes microbe-produced nutrients
like propionate in fasted and fed states for energy and metabolite production. In isolation, microbe-produced
nutrients and BCAAs are known to stimulate the secretion of peptide incretin hormones from nutrient sensing
cells lining the lumen that coordinate whole body metabolism in preparation for a nutrient load. Incretin response
and enteric glucose metabolism are reduced in obese and diabetic patients but the mechanisms driving
dysregulation are poorly understood. Synergy between microbe-produced and dietary nutrients could contribute
to incretin dysregulation and/or alter enteric metabolic effecting circulating metabolite pools. Directly measuring
the metabolism of dietary and circulating BCAAs will quantify the contribution of intestine metabolism to
circulating BCAA and metabolite pools. Determining if intestine BCAA metabolism interacts with the metabolism
of microbiota-produced nutrients and sucrose will show if intestine metabolism contributes to the elevated BCAA
and metabolite pools associated with metabolic disease.
Candidate/Training: Long term, I plan to pursue an independent research career managing an interdisciplinary
laboratory developing probiotics and/or pharmaceuticals that change intestine nutrient handling to treat metabolic
disease. In pursuit of this goal, I have assembled research aims and a mentoring team to provide me with the
foundational knowledge and training essential to my progress. Dr. White, an expert metabolic physiologist with
many high-profile publications on BCAA metabolism in other tissues, will balance the more microbiology-driven
mentorship provided by Dr. John Rawls. We have detailed the technical skills I will gain through their training or
formal courses and detailed the community meetings I will attend to build the necessary skills to transition to
independence. A larger committee including the directors of Duke’s Metabolic Physiology Institute and
Microbiome Center as well as the Chief of the Division of Gastroente...

## Key facts

- **NIH application ID:** 11010919
- **Project number:** 4R00DK132554-03
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Ian Andrew Williamson
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11010919

## Citation

> US National Institutes of Health, RePORTER application 11010919, Quantifying Enteric Metabolism of Branched-chain Amino Acids in Relation to Other Dietary and Microbiota Nutrients (4R00DK132554-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11010919. Licensed CC0.

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