The group found that the gene "CGI-58" is a strong activator of one of three lipid-degrading enzymes, or lipases, that disassemble triacylglycerol. Triacylglycerol is perhaps more commonly known as triglycerides. In vertebrates including humans, excess nutritional carbohydrates and fat are efficiently converted into triglycerides and deposited in fat tissue.
The team, led by Rudolf Zechner of the University of Graz in Austria, now reports that CGI-58 boosts the activity of so-called adipose triglyceride lipase (ATGL) up to 20-fold.
"We knew that the enzyme responsible for CDS must be very important for fat breakdown, but its involvement in neutral lipid catabolism remained unexplained," Zechner said. "The discovery that CGI-58 acts as a very potent activator offers a new picture of how stored fat is broken down in adipose and other tissues."
The finding solves a puzzle first raised in 2001 with the discovery that CGI-58 caused the lipid storage disease CDS in some patients, Zechner said. The symptoms characteristic of the disorder coupled with the structure of the enzyme encoded by CGI-58 led researchers to suspect that the enzyme itself acted as a lipase. However, studies failed to confirm its lipid-busting activity and its role remained mysterious.
Triglycerides consist of three fatty acids, each of which is removed in a "step-wise affair" from its glycerol backbone, Zechner explained. One of the lipases responsible, hormone-sensitive lipase, was discovered decades