# Orexin and serotonin interactions to promote physical activity and prevent obesity

> **NIH VA I01** · MINNEAPOLIS VA  MEDICAL CENTER · 2021 · —

## Abstract

The overall goal of this proposal is to identify strategies that target the orexin brain network that
regulates spontaneous physical activity, and the associated caloric expenditure. This energy
expenditure is referred to as non-exercise activity thermogenesis (NEAT), and we propose that this
can be exploited to develop new therapies for weight gain prevention and weight loss in those unable
to exercise. The specific objectives are to determine which sub-population of orexin neurons are
associated with the most robust effect on NEAT; whether therapy length influence the effectiveness of
this targeted NEAT therapy; and finally, whether serotonin in a specific brain area, the dorsal raphe
nucleus (DRN), modulates the calories produced by this targeted NEAT therapy. The significance is
the potential to discover a new therapy for Veterans needing to lose weight or for preventing weight
gain in Veterans with limited options for formal exercise, thus reducing the burden of obesity and
associated co-morbidities. Drugs targeting orexin and serotonin receptors are already clinically
available, providing proof-of-concept that these drugs could be successfully manipulated for human
health. The novelty lies in the idea to create a therapy based on promotion of NEAT; our newly
established methods to study brain networks using Designer Receptors Exclusively activated by
Designer Drugs (DREADDs); our animal models for studying orexin, a neuropeptide that significantly
increases NEAT; and newly obtained equipment for allowing sophisticated quantification of NEAT.

## Key facts

- **NIH application ID:** 10045949
- **Project number:** 5I01BX003687-04
- **Recipient organization:** MINNEAPOLIS VA  MEDICAL CENTER
- **Principal Investigator:** Charles J. Billington
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045949

## Citation

> US National Institutes of Health, RePORTER application 10045949, Orexin and serotonin interactions to promote physical activity and prevent obesity (5I01BX003687-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10045949. Licensed CC0.

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