Fundamental Breakthrough Could Lead to Treatments for Obesity

If you tend toward obesity, blame your genes. Scientists at the Albert Einstein College of Medicine have discovered how the genes and proteins that cause your body to store fat - or use it - work. Organisms from yeast to humans all share the ability to store fat within cells, and now one of the main mechanisms and the potential for regulating that metabolic pathway seems possible.

"The identification of FIT proteins should facilitate the development of reagents to regulate FIT expression or activity to treat diseases associated with excessive lipid droplet accumulation, such as obesity, type 2 diabetes, and atherosclerosis," the researchers concluded.

Some of the genes causing the storage of fat have been known for several years, but which genes and how the genes work together to create the drops of lipids (fat) within cells was unknown. This is a fundamental breakthrough in understanding the mechanism that can lead to life-threatening obesity, as well as follow-on conditions such as type 2 diabetes and atherosclerosis.

The team led by Dr. David L. Silver identified two genes responsible for the formation of fat droplets, which they have named FIT1 and FIT2 (for Fat-Inducing Transcripts 1 and 2). Silver is an assistant professor at Yeshiva University whose primary research efforts are in the molecular mechanisms of lipid metabolism. These genes apparently control the formation of all forms of triglycerides, not just the type that is made and stored.

One of the fundamental discoveries was that by "knocking out" FIT2 (in a genetically modified mouse that does not have the gene), the formation of fat droplets was significantly reduced. Because these genes are ubiquitous and common across a vast array of species, Silver's group was able to study the effects of the genes, or their suppression, in both fish and mice, with similar results.

"Now that we've identified the genes and the proteins they code for, it should be possible to develop drugs that can regulate their expression or activity," Silver said in an interview with Science Daily. "Such drugs could prove extremely valuable, not only for treating the main result of excess lipid droplet accumulation--obesity--but for alleviating the serious disorders that arise from obesity including type 2 diabetes and heart disease."

Co-authors were lead author Bert Kadereit, Pradeep Kumar, Wen-Jun Wang, Diego Miranda, Erik L. Snapp, Nadia Severina, Ingrid Torregroza and Todd Evans. Work was funded in part by grants from the National Institutes of Health.