# Body weight control by hypothalamic OGT

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $652,546

## Abstract

Project Summary/Abstract
The central nervous system plays a pivotal role in metabolism, within which the ventromedial
hypothalamus (VMH) is crucial for proper regulation of body weight and blood glucose level. The VMH
senses nutrients and circulating hormones and integrates its metabolic information to coordinate effector
responses to maintain organismal homeostasis. O-linked beta-D-N-acetylglucosamine (O-GlcNAc)
modification, catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and
hormones. Our recent studies reveal that OGT in the VMH is required for promoting adipose tissue
lipolysis and maintaining energy balance by regulating the VMH neuronal activity and sympathetic
innervations to white adipose tissues. Based on these findings, we hypothesize that VMH O-GlcNAc
signaling determines a body weight setpoint by means of humoral and nutritional sensing and filtering
lipolytic information to white adipose tissues. To test this hypothesis, we will combine gain- and loss-of-
function models with state-of-the-art neural tracing and molecular profiling tools, optogenetic and
electrophysiological recordings, and comprehensive physiological assessments to delineate the
mechanisms by which VMH OGT regulates adipose tissue function and constrains body weight gain. Aim
1 will determine whether O-GlcNAc signaling in VMH neurons determines the setpoint of body weight.
Aim 2 will delineate the neurocircuitry by which OGT-expressing VMH neurons relay lipolytic information
to white adipose tissues. Aim 3 will identify how O-GlcNAc signaling regulates hormonal and nutritional
sensing of VMH neurons. A detailed understanding of body weight control by hypothalamic OGT could
support the development of novel therapies for obesity and co-morbidities.

## Key facts

- **NIH application ID:** 10912799
- **Project number:** 5R01DK137467-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Xiaoyong Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $652,546
- **Award type:** 5
- **Project period:** 2023-08-25 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912799

## Citation

> US National Institutes of Health, RePORTER application 10912799, Body weight control by hypothalamic OGT (5R01DK137467-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10912799. Licensed CC0.

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