# Neural mechanisms in high fat diet impairment of brown adipose tissue activity

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $424,553

## Abstract

Project Summary
 The sympathetic activation of brown adipose tissue (BAT) increases the metabolism of
fatty acids within this tissue. Due to the presence of uncoupling protein-1 in the mitochondria of
BAT the electrochemical gradient generated by the electron transport chain is dissipated in the
absence of the production of ATP. This process which is unique to BAT (as well as inducible
forms of BAT, “beige” adipose tissue) in essence metabolizes fat to produce heat. The obvious
implications of this “fat burning” process for energy balance and body weight regulation have led
to intense interest in the biological mechanisms governing this process. The activity of the
sympathetic nerves innervating BAT is the principal regulator of this process. Our research has
defined the fundamental neural pathways through which thermal and febrile stimuli elicit
changes in the sympathetic outflow to BAT. However, relatively little is known about the neural
circuits involved in the metabolic influences on BAT and how dietary components (such as the
fat content of the diet) influence these regulatory circuits.
 In the proposed research project, we will perform an extensive series of in vivo and in
vitro electrophysiological, anatomical, neuropharmacological, and Designer Receptors
Exclusively Activated by Designer Drugs (DREADDs) experiments to address specific aims that
will provide new insights into the neural mechanisms responsible for the impairment of BAT
activation during high fat diet (HFD) and the specific contribution of this impairment to HFD-
induced weight gain. The first aim will determine the role of transient receptor potential vanilloid
type 1 (TRPV1) in NTS in the impairment of BAT activation during maintenance on a high fat
diet. The second aim will define the downstream projection target of the NTS that is responsible
for inhibition of sympathetic output to BAT during HFD. The third aim will define the role of
preprodynorphin neurons in the lateral parabrachial nucleus and kappa opioid receptor
activation in the preoptic area in the impairment of BAT activation during HFD. The forth aim will
define the output projection target and neurophysiological characteristics of kappa opioid
receptor containing neurons of the preoptic area.

## Key facts

- **NIH application ID:** 10063993
- **Project number:** 5R01DK112198-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** CHRISTOPHER J MADDEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $424,553
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063993

## Citation

> US National Institutes of Health, RePORTER application 10063993, Neural mechanisms in high fat diet impairment of brown adipose tissue activity (5R01DK112198-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10063993. Licensed CC0.

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