# Role of Brown Adipose Tissue Thermogenesis in Oxytocin-Elicited Weight Loss in Rodents and Nonhuman Primates

> **NIH VA I01** · VA PUGET SOUND HEALTHCARE SYSTEM · 2020 · —

## Abstract

Central leptin resistance results in decreased downstream signaling to brain circuits that regulate food intake
and energy expenditure (EE), thereby promoting hyperphagia and obesity. 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 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 nervous system (SNS) 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 DIO rats. We will also determine if sympathetic outflow to both IBAT and white adipose
tissue (WAT) mediates the effects of OT on EE by testing the extent to which pharmacological blockade of
beta-3 adrenergic receptors (β-3-AR) impairs the ability of 4V OT administration to increase EE in DIO rats. In
addition, we will determine if OT can be combined with low doses of the β-3-AR agonist, CL316243, to
increase EE and promote weight loss in DIO rats. Endpoints will include EE, IBAT temperature, norepinephrine
turnover (NETO; marker of sympathetic activity), food intake, body composition (total and relative fat mass,
lean mass), and BW. We anticipate these studies to establish a key role for SNS outflow to IBAT in the
mechanism by which OT increases EE and elicits BW loss in DIO rats. In Specific Aim 2 we will test the
hypothesis that in DIO rhesus monkeys, intranasal OT reduces BW and improves glucose tolerance and other
metabolic parameters, in part, by stimulating SNS outflow to BAT. To accomplish this, we will determine if
intranasal OT increases the temperature of axillary BAT (ABAT, the predominant BAT depot found in rhesus
monkeys) at a dose that elicits weight loss in DIO NHPs. We will also determine the extent to which intranasal
OT elicits weight loss by reducing body adiposity while sparing lean mass and identify if these effects are
associated with improvements in glucose tolerance. We will further identify if intranasal OT may also increase
SNS outflow to WAT by measuring changes in subcutaneous WAT temperature and uncoupling protein-1
protein expression in subcutaneous WAT relative to ABAT (pre- and post-intervention). If we find that
intranasal OT increases EE and BAT thermogenesis in the NHP model, these studies will provide evidence for
a rol...

## Key facts

- **NIH application ID:** 9859334
- **Project number:** 5I01BX004102-03
- **Recipient organization:** VA PUGET SOUND HEALTHCARE SYSTEM
- **Principal Investigator:** James Ernest Blevins
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859334

## Citation

> US National Institutes of Health, RePORTER application 9859334, Role of Brown Adipose Tissue Thermogenesis in Oxytocin-Elicited Weight Loss in Rodents and Nonhuman Primates (5I01BX004102-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859334. Licensed CC0.

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