# Measuring Lipid Flux By Ultra High Resolution Mass Spectrometry

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $408,750

## Abstract

Project Summary:
 Many human diseases are caused by a dysregulation of lipid metabolism, including atherosclerosis,
cancer, neurodegeneration, diabetes, and fatty liver. The development of effective treatments for lipid related
disorders is hinder by a lack of modern in vivo biochemistry techniques for studying lipid metabolism. The
overall goal of this proposal is to develop tools and protocol to measure the rates of lipid biosynthesis and
remodeling by stable isotope labeling with sensitivity comparable to radio-isotope tracing with the specificity
and broad coverage of modern mass spectrometry based lipidomics. This is enabled by an ultra-high
resolution orbitrap mass spectrometer I developed in collaboration of Thermo Scientific, now commercially
available as the Lumos 1M. This instrument has sufficient resolution to resolve the natural abundance 13C
from a tracer isotope, for example 2H, in intact lipid ions. By resolving the dominant natural abundance ions
from tracer isotopes will improve the signal to noise ratio by at least 2 orders of magnitude (1:1 vs >1:100) and
increase the dynamic range. This advancement will allow in vivo analysis of lipid metabolism to study a
variety of disease, and will ultimately lead to lipid fluxomics analysis that is translatable to human studies. By
measuring lipid flux in patients we will be able to directly studying the progression of metabolic syndrome,
potentially circumventing the need for animal models, and measure the effectiveness of therapies and
interventions.
 To facilitate the development and widespread implementation of this technology, I will address the
fundamental roadblocks to adapting this technology. Firstly, the commercial instrument is engineered for
proteomics applications, in particular the electrospray ionization source. By working with the manufacturer and
translating my lipidomics experience to this new platform I will overcome these issue. Secondly, I will develop
novel data collection approaches for both chromatography and direct infusion based applications to
accommodate the long transient time and coalescence issues associated with ultra-high resolution resonance
based mass spectrometry. Thirdly, software tools will be developed to extract ultra-high resolution data in a
time efficient manner, convert the data to physically interpretable parameters, and map data onto biochemical
pathways. Lastly, I will develop protocols and platforms for stable isotope labeling by deuterium labeled water
(D2O) and other isotope labeled metabolic tracers in mouse models of metabolic syndrome relevant to my lab’s
research program studying the mechanism for fat accumulation. By accomplishing these aims this technology
will be accessible to the biomedical research community. My multi-disciplinary training in engineering,
physical, analytical and biochemistry, and mouse genetics makes me well-suited to develop this technology
and the lipid centric research environment at UT Southwestern is the idea...

## Key facts

- **NIH application ID:** 10027699
- **Project number:** 1R35GM137991-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Matthew Alvin Mitsche
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,750
- **Award type:** 1
- **Project period:** 2020-09-05 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10027699

## Citation

> US National Institutes of Health, RePORTER application 10027699, Measuring Lipid Flux By Ultra High Resolution Mass Spectrometry (1R35GM137991-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10027699. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*