# Mass Spectrometric Studies of Neuropeptides in Feeding

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $404,437

## Abstract

PROJECT SUMMARY/ABSTRACT
Feeding behavior is critical for animal survival, and is also a fundamental aspect of energy homeostasis. This
process is regulated by highly complex neurochemical pathways involving a multitude of neuropeptides and
biogenic amines. Despite decades of work on individual neurochemical systems, the general organizational
principles underlying neuromodulation are still poorly understood. This is mainly due to the fact that
modulation of neural circuit has so far been studied primarily one modulator at a time without the knowledge
about co-modulation of networks. The latter information would require the development of sensitive and
selective analytical tools to precisely identify these low abundance endogenous signaling molecules and
accurately measure their behaviorally-relevant concentrations in a complex microenvironment. Our proposed
research aims to address this critical knowledge and technological gap by developing new bioanalytical
methods to elucidate the complex identities and functional roles of neuropeptides in food intake via combined
mass spectrometric and physiological approaches. We employ the crustacean stomatogastric nervous system
and its associated neuroendocrine organs as a test-bed for technology development and validation due to the
unique advantages and biological significance of this model system. In parallel, we aim to translate our
technology development for neuropeptide discovery and analysis to the mammalian central nervous system.
To this end, we propose to focus on key brain regions in a rat model at progressively more complex levels of
feeding-related information processing. The specific aims include: (1) Developing a set of novel mass defect-
based multiplex dimethyl pyrimidinyl ornithine (DiPyrO) tags for accurate and high throughput MS1-based
relative quantification of in vivo expression changes of neuropeptides under different feeding conditions; (2)
Developing a sub-ambient ionization MALDI-based mass spectral imaging (MSI) technique for mapping
neuropeptides and amine neurotransmitters in identified neurons and feeding circuits, with enhanced spatial
resolution and speed; (3) Developing a multi-target affinity-enhanced microdialysis in vivo sampling technique
for MS detection and quantitation of circulating neuropeptides and biogenic amines in response to food intake,
via a novel hybrid absolute and relative quantification (HARQ) strategy using isobaric dimethylated leucine
(DiLeu) and isotopic DiLeu tags; and (4) Determining the functional consequences of neuropeptide isoforms
and assaying functional activities of hormonal cocktails by combining mass spectrometric, electrophysiological,
and behavioral studies. Novel neuropeptides will be evaluated for functional roles in feeding regulation. The
outcome of the proposed research will be a suite of new analytical tools enabling quantitative assessment of
the interplay of neuropeptides and biogenic amines with high spatial, chemical and tempo...

## Key facts

- **NIH application ID:** 9931209
- **Project number:** 5R01DK071801-14
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** LINGJUN LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,437
- **Award type:** 5
- **Project period:** 2006-05-01 → 2022-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931209

## Citation

> US National Institutes of Health, RePORTER application 9931209, Mass Spectrometric Studies of Neuropeptides in Feeding (5R01DK071801-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9931209. Licensed CC0.

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