# Ano4 and Metabolic Health

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $509,969

## Abstract

PROJECT SUMMARY
Obesity is a major risk factor for many chronic medical conditions, including diabetes, cardiovascular disease,
depression, and cancer. Elucidating the neural mechanisms that regulate feeding behavior and body weight
control is critically needed towards the development of effective strategies to combat obesity and its co-
morbidities. We discovered that anoctamin 4 (Ano4, an ion channel) is abundantly expressed in the area
postrema (AP) in the hindbrain. Activation of these APAno4 neurons increase food intake and blood glucose in
mice. Importantly, a large-scale human genetic study established the association of the ANO4 gene mutation
with human obesity, but the causality of this association has not been tested. The first objective is to determine
physiological relevance of APAno4 neurons in energy/glucose balance. We will use both gain- and loss-of-function
models to establish the function of the APAno4 neurons on feeding and valence behavior, as well as long-term
regulation of body weight and glucose homeostasis. The second objective is to use a Cas9-mediated DNA editing
to delete Ano4 only in AP neurons, and to determine physiological functions of the Ano4 channel on the
excitability of AP neurons and on the whole-body energy/glucose balance. The third objective is to use a
humanized Ano4 knock-in mouse model (mimicking the obesity-associated human ANO4 mutation) to determine
whether this mutation causes obesity in mice and alters Ano4 channel functions. Completion of the proposed
research will identify a novel target that regulates body weight balance in mice and humans, and provide the
necessary framework to develop therapeutic strategies towards treating obesity.

## Key facts

- **NIH application ID:** 11072849
- **Project number:** 1R01DK139583-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** YONG XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $509,969
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11072849

## Citation

> US National Institutes of Health, RePORTER application 11072849, Ano4 and Metabolic Health (1R01DK139583-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11072849. Licensed CC0.

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