# Kansas Center for Metabolism and Obesity REsearch (KC-MORE) - Project 2

> **NIH NIH P20** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $290,600

## Abstract

PROJECT 2 (MORRIS): PROJECT SUMMARY
Obesity is the strongest independent predictor for the onset and progression of metabolic diseases, such as type
2 diabetes and cardiovascular disease. Weight gain occurs due combination of increased food/energy intake
and decreased total energy expenditure to create a positive energy balance. Energy balance is not constant or
consistent, and therefore long-term weight gain occurs as a sum of numerous, small positive fluctuations over
time scales ranging from days to seasons. These acute episodes of positive energy balance occur as a complex
interaction of the current obesogenic environment and inappropriate regulation of energy homeostasis. Energy
homeostasis is regulated through the integration of peripheral neural, hormonal and nutrient signals by a
complex, interconnected central network, including the ventromedial nucleus of the hypothalamus (VMH). The
VMH has been observed as involved in the regulation of both components of energy balance, energy expenditure
and energy intake, making it an important component of body weight regulation. The main goal of the proposed
3-year research plan is to establish an independent research line investigating the role of mitochondrial
lipid metabolism in ventromedial hypothalamus neurons on the regulation of energy homeostasis.
Activation of pathways involved in sensing reduced cellular energy state in the VMH have been proposed to
increase food intake through acute activation of neuron lipid metabolism. Further, inhibition of these same
pathways has been observed to increase whole-body energy expenditure. However, it is unknown whether
regulation of these two components of energy homeostasis is dependent upon mitochondrial lipid metabolism in
VMH neurons. The central hypothesis of this proposal is that neuronal mitochondrial lipid metabolism in the VMH
modulates systemic energy homeostasis regulation during exposure to energy dense diets through control of 1)
food intake and 2) energy expenditure. In this proposal, we will use a VMH-specific, PGC-1α knockout (VPGC1a-
/-) mouse model to study the role of neuron mitochondrial fatty acid oxidation and respiratory function on food
intake regulation during fasting and satiety hormone exposure. Additional studies will examine whether
modulation of neuronal mitochondria lipid metabolism impacts high-fat/high-sucrose-induced weight gain. As a
corollary, both sets of studies will utilize adeno-associated virus to increase mitochondrial lipid metabolism in
VMH neurons through overexpression of PGC1a.

## Key facts

- **NIH application ID:** 10335442
- **Project number:** 1P20GM144269-01
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** E Matthew Morris
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $290,600
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335442

## Citation

> US National Institutes of Health, RePORTER application 10335442, Kansas Center for Metabolism and Obesity REsearch (KC-MORE) - Project 2 (1P20GM144269-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10335442. Licensed CC0.

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