# Obesity in ciliopathies: How neuronal primary cilia control appetite

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $663,640

## Abstract

Project Summary/Abstract
 We investigate how neuronal primary cilia regulate energy homeostasis and how
their dysregulation causes obesity. Primary cilia are cell surface projections that receive
and transduce select intercellular signals. In humans, disruption of primary cilia function
causes ciliopathies, pleiotropic diseases of which obesity is a cardinal manifestation. The
most common monogenic cause of severe human obesity is mutation of MC4R, encoding
a hypothalamic GPCR that regulates energy homeostasis.
 In the initial funding period of this project, we have demonstrated that MC4R
localizes and functions at the primary cilia in vivo, and that its localization and function are
dependent on the MC4R-associated protein MRAP2. We also found that inhibiting
adenylyl cyclase in the primary cilia of MC4R neurons causes obesity. These findings
suggest that hypothalamic neurons use cilia to communicate through MC4R to regulate
energy homeostasis.
 Here, we build on these findings, and on new genetic and molecular tools we have
developed, to investigate how ciliopathies disrupt ciliary MC4R signaling, how the ligands
of MC4R regulate its localization to cilia, and how MC4R activity is transduced by the
cilium. Together, these experiments will illuminate how cilia signaling encodes long-term
energy homeostasis and how neurons use cilia to communicate non-synaptically.

## Key facts

- **NIH application ID:** 10906014
- **Project number:** 5R01DK106404-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jeremy F Reiter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $663,640
- **Award type:** 5
- **Project period:** 2016-06-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906014

## Citation

> US National Institutes of Health, RePORTER application 10906014, Obesity in ciliopathies: How neuronal primary cilia control appetite (5R01DK106404-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10906014. Licensed CC0.

---

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