# The dorsomedial hypothalamus integrates temperature and energy sensing signals to regulate energy expenditure.

> **NIH NIH F32** · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2022 · $69,629

## Abstract

ABSTRACT
The two primary factors that drive changes in body weight (BW) - food intake (FI) and energy expenditure (EE)
- are both regulated within the hypothalamus of the brain and respond to changes in energy availability
(energy-sensing) and ambient temperature (temperature-sensing). A more comprehensive understanding of
how the hypothalamus regulates food intake and energy expenditure can enhance our approach to treating
obesity through a pharmaceutical and/or environmental approach that targets the relevant neurons and/or
environmental strategies that promote high EE and lower FI. Research outlined in this proposal seeks to
describe how temperature and energy-sensing circuits integrate with each other. Proopiomelanocortin (POMC)
and agouti-related peptide (AgRP) neurons in the arcuate nucleus (ARC) are known to regulate FI via MC4R
signaling in the paraventricular nucleus (PVN), but the PVN does not account for EE regulation in response to
feeding signals (2). An article investigating Gsα deficiency in the DMH revealed that DMH-specific MC4R
knockout impairs EE and resulted in BW increases without impacting FI, implying that energy-sensing signals
from the ARC affect EE adaptations via the DMH (3). Our hypothesis is that the DMH is an integration site
of thermoregulatory and energy-sensing signals that impact EE. Activation of warm-sensitive neurons of
the preoptic area suppresses EE in response to warm temperatures, and this is traditionally thought to occur
via the inhibition of cold-sensitive neurons in the DMH that promote brown adipose tissue (BAT) thermogenesis
despite the recent discovery that warm sensitive POA neurons are glutamatergic (6). Additionally, the POA
projects directly to sympathetic pre-motor neurons in the raphe pallidus (RPa), and it is unclear what distinctive
roles the POA-DMH and POA-RPa connection play in EE regulation (5). We hypothesize that the POA-DMH
connection is a critical integrator for temperature and energy state EE adaptations, while the POA-RPa
might mediate only temperature-dependent EE adaptations and could bypass feeding-induced MC4R
signaling in the DMH. Using optogenetics and a novel strategy known as synthetic-and-physiological-
activation-assisted-circuit-mapping (SPAACM), we will investigate how the POA, DMH, RPa, and ARC interact
with each other and control EE in response to changes in ambient temperature and feeding states. SPECIFIC
AIM I investigates the role of energy-sensing signals in the DMH and whether there is a temperature-
dependent effect on EE within this circuit. SPECIFIC AIM II focuses on the POA>DMH and POA>RPa
connections and their respective contributions to thermoregulatory modulation of EE.

## Key facts

- **NIH application ID:** 10464727
- **Project number:** 1F32DK132863-01
- **Recipient organization:** LSU PENNINGTON BIOMEDICAL RESEARCH CTR
- **Principal Investigator:** Sean Swetledge
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,629
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-04-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464727

## Citation

> US National Institutes of Health, RePORTER application 10464727, The dorsomedial hypothalamus integrates temperature and energy sensing signals to regulate energy expenditure. (1F32DK132863-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10464727. Licensed CC0.

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