# Deciphering the role of miR-33 in central regulation of feeding behavior

> **NIH NIH K01** · YALE UNIVERSITY · 2020 · $155,346

## Abstract

PROJECT SUMMARY/ABSTRACT
This is an application for a KO1 Award for Nathan Price Ph.D., an associate research scientist at Yale Medical
School. His research focuses on identifying novel factors involved in the regulation of cellular bioenergetics and
determining how these factors contribute to the development of diseases associated with obesity, aging, and
metabolic syndrome. The primary objectives of the proposed research are (1) to determine how loss of miR-33
in AgRP neurons impacts regulation of metabolic homeostasis by the brain, (2) establish the specific
mechanisms by which miR-33 mediates these effects, and (3) provide Dr. Price with the experience and skills
necessary to establish himself as an independent investigator and pursue his future research goals. Prior work
has established miR-33 as an important regulator of lipid metabolism, mitochondrial function, and fatty acid
oxidation, and demonstrated the effectiveness of anti-miR-33 therapeutics for the treatment of cardiovascular
disease in animal models. However, recent work has demonstrated that whole body loss of miR-33 results in a
strong predisposition to the development of obesity and metabolic dysfunction, due to increased food intake.
Regulation of feeding behavior by the brain is primarily mediated through AgRP and POMC neurons, which
promote signals of hunger and satiety, respectively. The proposed research strategy will utilize a newly
developed mouse model that lacks miR-33 in AgRP neurons, which are responsible for promoting feeding
behavior. The preliminary data provided indicate that loss of miR-33 in AgRP neurons promotes obesity and
metabolic function in a manner similar to whole body miR-33 deficiency. This work will involve an in-depth
analysis of the specific impact of miR-33 in AgRP neurons on the regulation of feeding and obesity, and
determine the mechanisms by which miR-33 mediates these effects. Utilization of cutting edge techniques for
identifying changes in actively translated mRNAs only in AgRP neurons will allow us to identify miR-33 targets
that have increased expression in AgRP neurons lacking miR-33. Furthermore, we will be able to assess the
likelihood that these genes are involved in mediating the effects of miR-33 on obesity and metabolic function by
selectively knocking down specific target genes only in AgRP neurons. This work will provide an improved
understanding of the mechanisms by which miR-33 regulates obesity and metabolic function, and offer
necessary insight into possible new mechanisms for the treatment of metabolic diseases. The proposed
research will also facilitate Dr. Price’s growth as a researcher by providing experience in studying central
regulation of metabolism, and promoting the development of new skills that can be utilized in his future research.
Dr. Price’s mentors and collaborators will oversee his training in these areas, and provide the expertise and
experience necessary to carry out the proposed research. They, along with...

## Key facts

- **NIH application ID:** 9892727
- **Project number:** 1K01DK120794-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Nathan Price
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,346
- **Award type:** 1
- **Project period:** 2020-01-01 → 2020-11-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892727

## Citation

> US National Institutes of Health, RePORTER application 9892727, Deciphering the role of miR-33 in central regulation of feeding behavior (1K01DK120794-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9892727. Licensed CC0.

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