# Targeting olfactory neural pathways to combat obesity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $543,322

## Abstract

PROJECT SUMMARY
The sense of smell mainly plays a priming role in eating behavior. Recently, we observed that relatively long
time food (chow)-derived odor exposure suppresses both chow and high fat diet intake in mice. Further, we
found that a subset of neurons in the ventral subiculum (vSub) are activated by food odor and send monosynaptic
projections to the ventromedial hypothalamus (VMH). Additionally, we found that inhibition of these neurons
attenuated the hypophagic response induced by food-derived odor exposure. Based on this, the first objective
of this proposal is to determine the physiological relevance of food odor-responsive vSub neurons in regulation
of food intake. Noteworthy, we will determine the transcriptomic features of food odor-activated vSub neurons,
which could potentially identify a novel neuron population that govern olfactory sensation-regulated feeding
behavior. Using chronic activation and inhibition model, the second objective is to explore the long-term
implications of vSub → VMH circuit in body weight regulation. We also discovered that VMH-projecting vSub
neurons receive strong synaptic inputs from OB neurons. Furthermore, we observed that activation of vSub-
projecting OB neurons suppresses food intake and body weight gain. Building on this observation, the third
objective is to elucidate the functional sufficiency and necessity of the OB→ vSub→ VMH circuit in the regulation
of systemic energy homeostasis.
The current proposal aims to determine how the olfactory bulb (OB)-originated neural circuits mediate food-
derived odor-induced satiety. Our studies will advance our current understanding about the sensory inputs in
regulating feeding behavior. This may facilitate development of novel therapies for related human diseases, such
as obesity and eating disorders. Therefore, this proposed research is directly relevant to public health and the
NIH’s mission.

## Key facts

- **NIH application ID:** 10946430
- **Project number:** 1R01DK140538-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Yang He
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $543,322
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10946430

## Citation

> US National Institutes of Health, RePORTER application 10946430, Targeting olfactory neural pathways to combat obesity (1R01DK140538-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10946430. Licensed CC0.

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