New Insights into Gpr45 Gene Activity in Brain Cilia Reveal Potential Targets for Obesity Treatment

Researchers at UT Southwestern Medical Center have uncovered a critical genetic pathway involved in appetite regulation, focusing on the Gpr45 gene's activity within brain cell primary cilia. Using innovative tools like Automated Meiotic Mapping (AMM), they identified mutations in Gpr45 that contribute to overeating and obesity in mice. Further experiments confirmed that the absence of GPR45, the protein expressed by Gpr45, disrupts the transport of Gαs into primary cilia of hypothalamic neurons, impairing the activation of MC4R—a receptor crucial for controlling hunger. This disruption results in increased food intake and weight gain.

The study also highlights that proteins localized in primary cilia play vital roles in regulating feeding behaviors. Mutations affecting these proteins are linked to pediatric obesity and ciliopathies. The discovery suggests that boosting GPR45 activity may serve as a novel approach for developing anti-obesity therapies, especially since current drugs targeting the MC4R pathway are limited to rare genetic cases.

Published in Science, this research opens new avenues for understanding the genetic and cellular mechanisms underlying overeating. It emphasizes the importance of primary cilia in appetite regulation and presents potential new targets for pharmacological intervention to combat obesity, one of the most pressing health issues worldwide.

source: https://medicalxpress.com/news/2025-06-discovery-gpr45-gene-brain-cilia.html