# MCHergic control of feeding and energy balance in the LH area

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $433,403

## Abstract

Obesity, referring to having an abnormally high proportion of body fat, has become a health and economic
problem in wealthy countries such as the United States. Therefore, intensive investigations have been
conducted to determine the factors leading to the positive energy balance between energy intake and energy
expenditure. The hypothalamus plays a substantial role in the regulation of energy intake and expenditure.
However, it is still not clear how various neuronal systems in the hypothalamus interact to maintain normal
body weight and how the dys-regulated interactions may compromise the balance between energy intake and
expenditure. In this application we propose to identify interactions between melanin-concentrating hormone-
synthesizing (MCH) neurons and hypocretin (Hcrt) neurons in the lateral hypothalamus in the regulation of
energy balance and body weight at molecular, cellular and whole animal levels. Both MCH and Hcrt systems
are critical players in the regulation of energy balance in animals and humans. The MCH system promotes
energy intake and decreases energy expenditure while the Hcrt system promotes both energy intake and
expenditure. There has been morphological and functional evidence on the possible interactions between
these two systems. However, it is still not entirely clear whether the interaction between these two systems is
required in the regulation of energy balance in animals and humans and whether changes in the interaction
may lead to altered responses of the brain to the energy status of organisms and compromised energy
metabolism. Based on current data we hypothesize that a crosstalk between MCH and Hcrt systems is
required to maintain normal body weight. Specifically, we propose that the MCH system requires activation
from Hcrt cells to promote energy intake, while MCH neurons may provide a feedback pathway to limit the
activity in the Hcrt system to curb energy expenditure and maintain the normal body weight in animals. Since
neuronal plasticity plays a critical role in the formation and modification of homeostatic and behavioral
functions in animals, it is very likely that the modulation of synaptic function in MCH and Hcrt neurons could be
one of the mechanisms underlying the interaction between these two systems. Therefore, three goals of this
application are: 1) To test the hypothesis that MCH-mediated food intake requires activation from the Hcrt
system in animals.; 2) To interrogate the hypothesis that the MCH system is required to limit activity in the Hcrt
system to curb energy expenditure; and 3) To examine whether the imbalance between the activities in MCH
and Hcrt cells underlie dys-regulated metabolic status (DIO and anorexia) in animals. The answers to these
questions will help address the crosstalk between homeostatic centers in the hypothalamus and the role of the
crosstalk in the determination of energy metabolism. We hope that this project will benefit people suffering from
diseases/conditions ...

## Key facts

- **NIH application ID:** 10071382
- **Project number:** 1R01DK120891-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** XIAO-BING GAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,403
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071382

## Citation

> US National Institutes of Health, RePORTER application 10071382, MCHergic control of feeding and energy balance in the LH area (1R01DK120891-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071382. Licensed CC0.

---

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