Functional Analysis of Cilia's Role in Obesity

Cilia are hair-like structures that extend from nearly every cell in mammals. Non-motile cilia are involved in the sensations of the external environment, including light, smell and touch. Improper function of cilia is linked to a growing list of human disorders, including kidney disease, blindness, loss of the sense of smell, loss of left-right body asymmetry, male and female infertility, diabetes and obesity. Bardet-Biedl syndrome is an inherited disorder characterized by mental retardation as well as many of the symptoms linked with improper function of cilia. The known link between Bardet-Biedl syndrome and obesity demonstrates that dysfunction of cilia can predispose an organism to accumulate fat. How this occurs is unknown. However, people with this disorder are known to have an increased appetite and raised levels of certain types of proteins produced by fat cells that are involved in the regulation of appetite. Using a worm, Caenorhabditis elegans, which has sensory cilia remarkably similar to those of human cells, Michael Healey is aiming to clarify the role of ciliated nerve cells in regulating lipid levels. Healey is investigating whether all ciliary proteins or only a specific subset are involved in fat regulation, which ciliated nerve cells are important for fat regulation, and how cilia can control body weight. Ultimately, he aims to understand how Bardet-Biedl syndrome patients become obese, which will provide new insight into body weight control and the development of treatments for obesity.