A team of scientists in Germany has discovered a previously unknown gene in fruit flies that controls the metabolism of fat and showed that flies that have a defect in this gene, which they call “schlank” (the German for slim or lean), lose the ability to store fat in their bodies: the scientists say this discovery may lead to new treatments for obesity in humans because mammals have a group of genes that are structurally very similar to “schlank”.
The discovery was the work of Professor Michael Hoch from the University of Bonn, and colleagues, and is published online in The EMBO Journal on 15 October.
A Drosophila fruit fly with a normal schlank gene builds up fat reserves. But as Hoch explained:
“Larvae with a mutation of schlank, however, remain slim.”
“In extreme cases the defect can even lead to death,” he added.
Hoch, a development biologist, and colleagues decided to investigate the underlying mechanism of schlank.
They discovered that “schlank is involved in the de novo synthesis of a broad range of ceramides, the key metabolites of sphingolipid biosynthesis”.
Ceramides are raw materials for the gauzy membranes that surround all the cells in the body. But they do more than hold the cell together, they also send signals that regulate the synthesis of lipids (fats), while at the same time controlling the movement of fat from fat reserves.
The researchers decided to investigate if this was also the case in mammals: humans and other mammals also produce enzymes that make ceramides (so-called ceramide synthases), except unlike Drosophila which only has one ceramide synthase, humans have six different ones.
In humans and other mammals, ceramide synthases are regulated by another group of genes called the Lass gene, defects in which can lead to severe metabolic disorders and organ malfunction.
The Lass gene has a surprisingly similar structure to to the schlank gene of the fruit fly: in fact they are so similar that Lass gene from mice can partially compensate for a defective schlank gene in fruit flies, said Hoch.
“We introduced a mouse Lass gene in mutant Drosophila larvae,” he explained.
“Normally the larvae died immediately after hatching. Thanks to the Lass gene they resumed building up body fat and survived until the next development stage,” added Hoch.
Hoch and colleagues said in their conclusion that:
“Our results identify schlank as a new regulator of the balance between lipogenesis and lipolysis in Drosophila.”
“Furthermore, our studies of schlank and the mammalian Lass2 family member suggest a novel role for ceramide synthases in regulating body fat metabolism,” they added.
Hoch said that due to the strong paralles between schlank and Lass demonstrated with this study, they think it very likely that the Lass genes of mammals are linked to the control of lipid metabolism.
“If this is the case they would be a promising approach for new medications for obesity,” he said.
“Schlank, a member of the ceramide synthase family controls growth and body fat in Drosophila.”
Reinhard Bauer, André Voelzmann, Bernadette Breiden, Ute Schepers, Hany Farwanah, Ines Hahn, Franka Eckardt, Konrad Sandhoff, Michael Hoch.
DOI:10.1038/emboj.2009.305
Source: University of Bonn.
Written by: Catharine Paddock, PhD