The first disease gene for obesity was discoverd in 1994 in mice.

Scientists at the University of Marburg working with the German National Genome Research Network (NGFN) have now made a significant breakthrough in understanding the function of the ATGL gene in fat metabolism. They have studied ‘knock-out mice’ whose ATGL gene had been ‘silenced’. 

“Among other things, we managed to demonstrate with knock-out mice weighing around 25 g that they had over 2 g more body fat than normal mice,” says animal physiologist Dr. Martin Klingenspor. “However, they were unable to reduce these surplus fat reserves and burn them off through their metabolism.” “Our animals also cooled down noticeably”, explains the biologist. “When we didn’t give them any food for just a few hours, their body temperature dived from around 38°C to just 27°C. Deprived of the ATGL gene they could no longer mobilize their fat reserves.”

The ATGL gene provides the building instructions for a protein that plays a part in fat metabolism. Fat is usually stored in the body in the form of triglycerides, which are converted into free fatty acids. Free fatty acids are in turn used as an energy source by the body. Mice whose ATGL gene has been knocked out find it very difficult to break down the triglycerides. As a result, the fat deposits can no longer be reduced – the mice accumulate fat and become obese.

Even taking the genetic factors into account, the current thinking is that obesity is not solely due to genes in most cases but needs to be seen as a complex interaction between genetic material and an individual’s lifestyle, says Klingenspor. 

The research project run by the Marburg scientists is part of the National Genome Research Network (NGFN), which has been funded by the Federal Ministry of Education and Research (BMBF) since 2001.

Along similar lines to its counterpart in Germany, there is also a genome research program in Austria called GEN-AU, which was set up to study the structure and function of the human genetic makeup. Within the framework of this genome research initiative, there is also a project looking at the genomics of lipid-associated disorders (GOLD). Prof. Rudolf Zechner from the University of Graz coordinates this project.

“Our research findings are the fruit of close collaboration with Rudolf Zechner’s team,” says Klingenspor. “By networking GEN-AU and NGFN we have managed to bring together highly specialized techniques and expertise. Such collaboration is the only way of understanding the complex biological relationships that play a role in obesity.”