# Energy Homeostasis: GABAergic and Non-GABAergic POMC neurons

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $463,676

## Abstract

The hypothalamic neurons are major components of the neural circuits that control
energy homeostasis. Proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) play
a major role in regulating energy intake, energy expenditure, and glucose metabolism. In our
studies under the previous award from July 13, 2012 to present, we have clearly demonstrated
molecular and neurochemical heterogeneity of POMC neurons in the ARC and that distinct
subpopulations of POMC neurons directly and indirectly interact in a manner that is critical to
the net outcome of the melanocortin signaling. In addition to this neurochemical heterogeneity,
neuroanatomical studies have revealed that distinct sets of POMC neurons project to different
target sites. This neurochemical and neuroanatomical heterogeneity of ARC POMC neurons,
combined with their broad functional repertoire, strongly support the idea that there is functional
heterogeneity of ARC POMC neurons. As our specific aims under the previous award have
been completed, we now propose that neurochemically distinct subpopulations of POMC
neurons have distinct target organs and functions.
 The liver is the main glucose supplier in overnight fasting and short term fasting. Hepatic
glucose production results either from de novo synthesis via gluconeogenesis or from
degradation of hepatic glycogen via glycogenolysis. This process appears to be regulated by
the central melanocortin system. For instance, ARC POMC neurons project to liver and
postnatal ablation of POMC neurons elevates blood glucose levels and induces glucose
intolerance. However, there still exist foundational gaps in our knowledge of the neurobiology
and neuroanatomy of the central melanocortin system that regulates liver metabolism. Our
preliminary studies show that a subpopulation of ARC POMC neurons innervate liver through
two autonomic centers, including the intermediolateral cell column of the spinal cord and the
dorsal motor nucleus of the vagus. These neuroanatomical studies raise questions as to what
types of POMC neurons project to liver and which autonomic circuits are used by POMC
neurons to regulate hepatic glucose production. In fact, recent studies with genetically
engineered mice that have induced mutations exclusively in POMC neurons have demonstrated
that energy intake, energy expenditure, glucose metabolism, and locomotor activity are
regulated by distinct sets of POMC neurons. As there exist liver-projecting ARC POMC neurons,
we hypothesize that these liver-projecting ARC POMC neurons play a key role in the regulation
of hepatic glucose production. In Aim 1, we will thoroughly examine the neurochemical and
neuroanatomical identity of ARC POMC neurons projecting to liver. And then we will explore the
physiological impact of liver-projecting POMC neuron stimulation on hepatic glucose production
in Aim 2.
 In summary, we will incorporate optogenetics with viral-mediated delivery of the Cre
recombinase gene to achieve organ-specific opt...

## Key facts

- **NIH application ID:** 10201579
- **Project number:** 5R01DK092246-11
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** YOUNG-HWAN JO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $463,676
- **Award type:** 5
- **Project period:** 2012-07-13 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201579

## Citation

> US National Institutes of Health, RePORTER application 10201579, Energy Homeostasis: GABAergic and Non-GABAergic POMC neurons (5R01DK092246-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10201579. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*