# A Novel AgRP Neurons to the Dorsal Raphe Circuit in Control of Energy Expenditure

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $350,000

## Abstract

Project Summary:
Increasing amount of evidence indicate that hypothalamic AgRP neurons control energy homeostasis
by co-releasing NPY, AgRP and GABA to some specific post-synaptic targets in the brain. Recent
studies suggested that activation of AgRP neurons promotes weight gain by simultaneously
stimulating food intake and suppressing energy expenditure. However, it remains elusive as of how
AgRP neurons organize a neural circuit to suppress thermogenesis and reduce energy expenditure in
response to nutritional signals. The objective of this proposal is to gain mechanistic insights into the
functional connectivity and key signaling components of a novel AgRP circuit that exerts distinct
control of energy expenditure. Here, we obtained compelling results indicating that a subpopulation of
AgRP neurons exert unique control of intrascapular brown adipose tissue (iBAT) thermogenesis by
sending inhibitory projections to the ventral lateral part of the dorsal raphe nucleus (DRd) in the
midbrain. Our central hypothesis is that a subpopulation of AgRP neurons, in response to peripheral
nutritional signals, play a distinct role in suppression of energy expenditure by inhibiting MC4R-
expressing 5-HT neurons in the DRd. We will test the hypothesis in the following aims: Aim 1:
Determine whether a subset of AgRP neurons that project to the DRd plays a physiological role in
control of energy expenditure; Aim 2: Determine whether AgRP signaling mediates thermogenesis
and energy metabolism by suppression of MC4R signaling system in the DRd; Aim 3: Determine
whether serotonergic signaling in the DRd plays a crucial role in the regulation of AgRP neuron-
mediated energy expenditure. Our proposed studies will reveal mechanistic insights underlying the
control of thermogenesis and energy metabolism by a novel neural circuit. Taken together, the
potential outcome of proposed study would facilitate the elucidation of a more complete neural network
and underlying signaling pathways in distinct control of energy expenditure, one of the key
prerequisites to future development of effective treatment for obesity.

## Key facts

- **NIH application ID:** 9849244
- **Project number:** 5R01DK109194-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Qi Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,000
- **Award type:** 5
- **Project period:** 2017-01-04 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849244

## Citation

> US National Institutes of Health, RePORTER application 9849244, A Novel AgRP Neurons to the Dorsal Raphe Circuit in Control of Energy Expenditure (5R01DK109194-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849244. Licensed CC0.

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