# Influence of diet on the development of homeostatic neurocircuits

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $401,954

## Abstract

Project Summary/Abstract
The prevalence of obesity is increasing worldwide at a dramatic rate accompanied with an
ominous increase in comorbid conditions including Type 2 Diabetes, heart disease,
hypertension and hyperlipidemia. While it is increasingly accepted that obesity arises from a
combination of environmental, genetic and epigenetic factors, several lines of evidence have
suggested that the perinatal environment is critically important in the development of neural
circuits responsible for energy homeostasis and the integration of autonomic reflexes regulating
satiety. Vagally-mediated reflexes are recognized as playing a critical role in the neural
mechanisms of energy homeostasis. We have demonstrated previously that exposure to a high
fat diet (HFD) during the perinatal period (i.,e.., late pregnancy and lactation) decreases the
excitability and responsiveness of central vagal motoneurons; in the present proposal, we will
use a variety of electrophysiological, neurophysiological and physiological approaches to
investigate the novel overarching hypothesis that perinatal exposure to a high fat diet arrests the
developmental maturation of inhibitory neurocircuits within the brainstem.
Aim 1 will investigate the hypothesis that HFD exposure in the perinatal period induces
permanent changes in brainstem neurocircuits by arresting the developmental decline in
glycinergic synaptic inputs to dorsal motor nucleus of the vagus (DMV) neurons. Aim 2 will
investigate the hypothesis that the endogenous postnatal leptin surge is critical for the normal
developmental maturation of inhibitory vagal brainstem neurocircuits, and Aim 3 will investigate
the hypothesis that glucose regulates the excitability of DMV neurons from perinatal HFD, but
not control, rats due to positive allosteric modulation of glycine receptors.
The potential to examine permanent alterations in brainstem neurocircuitry resulting from diet-
induced disruption of leptin neurotrophic signaling in the perinatal period brings with it the
opportunity to uncover novel brain-gut neurosignaling pathways, the vulnerable time-points in
brainstem neurocircuit development, and neuromodulation and plasticity within vagally-
dependent reflexes which may be broadly applicable across autonomic homeostatic pathways.

## Key facts

- **NIH application ID:** 9840893
- **Project number:** 5R01DK111667-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Kirsteen Nairn Browning
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $401,954
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840893

## Citation

> US National Institutes of Health, RePORTER application 9840893, Influence of diet on the development of homeostatic neurocircuits (5R01DK111667-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840893. Licensed CC0.

---

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