# Integration of Lepr circuits for thermoregulation and energy status

> **NIH NIH R01** · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2020 · $370,000

## Abstract

Despite intense obesity research and growing knowledge of central and peripheral mechanisms that
modulate food intake and energy expenditure, lifestyle interventions to treat obesity have been consistently
unsuccessful in the long-term.
 Powerful physiological adaptations to fasting and food restriction oppose weight loss and are thought to
be the culprit that prevents long-term maintenance of weight loss. Yet, our understanding of these physiological
adaptations and the neuronal circuits involved is insufficient.
 Our work on leptin responsive neurons in the hypothalamus (POALepr and DMHLepr neurons) has
indicated that temperature sensing and energy sensing integrate in the same neuronal circuits that modulate
energy expenditure (EE) and food intake (FI). Furthermore, our data indicate that EE and FI are regulated
independent circuits.
 In line with this, we show compelling evidence that temperature and energy state greatly impact each
other due to explicit changes in neuronal activity within these circuits. Our working hypothesis integrates
known energy sensing circuits with temperature sensing circuits and highlights important changes in leptin
sensitivity that are not only impacted by energy sensing but also with ambient temperature, highlighting leptin
resistance as a physiological, rather than pathological condition. This novel view is an important progress for
our understanding of physiological adaptations that will be important for human and animal studies of
metabolism in health and disease.
The proposed experiments focus on the neuronal circuit integration of temperature-dependent and energy
state dependent changes in EE and FI.
 In Aim 1 we will investigate warm-sensing POALepr neurons that project to the DMH and their role to
suppress EE via cold-sensing DMHLepr. Furthermore, we will show that cold-sensing DMHLepr are also regulated
by energy sensing ARC neurons.
 In Aim 2 we will investigate warm-sensing POALepr neurons that project to the ARC and their role to
suppress FI via anorexigenic ARCPOMC neurons.
 In Aim 3 we will investigate the role of leptin and dynamic changes in leptin sensitivity to selectively
regulate EE via DMH-projecting Lepr neurons, while FI is regulated via PVN projecting Lepr neurons.

## Key facts

- **NIH application ID:** 10048883
- **Project number:** 2R01DK092587-06A1
- **Recipient organization:** LSU PENNINGTON BIOMEDICAL RESEARCH CTR
- **Principal Investigator:** Heike Muenzberg-Gruening
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,000
- **Award type:** 2
- **Project period:** 2012-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048883

## Citation

> US National Institutes of Health, RePORTER application 10048883, Integration of Lepr circuits for thermoregulation and energy status (2R01DK092587-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10048883. Licensed CC0.

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