# Role of Brown Adipose Tissue Thermogenesis in Oxytocin-Elicited Weight Loss

> **NIH NIH R01** · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · 2021 · $345,428

## Abstract

PROJECT SUMMARY/ABSTRACT
We and others have shown that the nonapeptide, oxytocin (OT), circumvents leptin resistance and elicits body
weight (BW) loss in diet-induced obese (DIO) rodents, nonhuman primates and obese humans, by reducing
both food intake and increasing energy expenditure (EE). The discovery of recruitable brown adipose tissue
(BAT) in humans has renewed interest in targeting BAT to elicit weight loss by increasing EE. OT neurons that
project directly from the parvocellular paraventricular nucleus (pPVN) to the hindbrain nucleus of the solitary
tract (NTS) are positioned to regulate energy homeostasis by reducing food intake and increasing BAT
thermogenesis. In Specific Aim 1 we will test the hypothesis that OT-induced stimulation of sympathetic
outflow to interscapular (IBAT) contributes to its ability to elicit weight loss in DIO rodents. To test this, we will
determine whether disrupting sympathetic activation of IBAT blocks the ability of fourth ventricular (4V) OT
administration to increase EE and elicit weight loss in male and female DIO rats. We will also determine if
sympathetic outflow to both IBAT and white adipose tissue mediate the effects of OT on EE by testing the
extent to which pharmacological blockade of beta-3 adrenergic receptors impairs the ability of 4V OT
administration to increase EE in male and female DIO rats. Endpoints will include EE, IBAT temperature
(TIBAT), norepinephrine turnover (NETO), food intake, and BW. We anticipate these studies to establish a key
role for sympathetic outflow to IBAT in the mechanism by which OT increases EE and elicits BW loss. In
Specific Aim 2 we will test the hypothesis that increased OT receptor (OTR) signaling within the NTS elicits
prolonged weight loss through distinct mechanisms that simultaneously reduce food intake and activate IBAT
to increase EE. To accomplish this we will reduce NTS OTR signaling by using both viral and pharmacological
approaches. This strategy will enable us to identify the extent to which these OTRs are required for effects of
both exogenous 4V OT administration and activation of endogenous OT signaling via chemogenetic excitation
of pPVN OT neurons, the sole source of endogenous OT relevant to sympathetic outflow. If we find that
disrupting NTS OTR signaling attenuates the ability of both exogenous and endogenous OT to reduce food
intake as well as increase EE, these studies will establish a key role for an OT-containing neurocircuit
projecting from pPVN to NTS in the control of energy balance. We also hypothesize that deficient NTS OTR
signaling mimics the metabolic and behavioral impairments associated with DIO and leptin resistance, and
abrogates the anti-obesity effect of chronic systemic OT treatment. To test this, we will administer a Cre-
expressing AAV into the NTS of Oxtrflox mice to ablate OTRs from NTS neurons and measure responsiveness
to systemic leptin or chronic systemic OT. Together, our findings will delineate whether NTS OTRs m...

## Key facts

- **NIH application ID:** 10101649
- **Project number:** 5R01DK115976-04
- **Recipient organization:** SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
- **Principal Investigator:** James Ernest Blevins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,428
- **Award type:** 5
- **Project period:** 2018-01-25 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101649

## Citation

> US National Institutes of Health, RePORTER application 10101649, Role of Brown Adipose Tissue Thermogenesis in Oxytocin-Elicited Weight Loss (5R01DK115976-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10101649. Licensed CC0.

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