Gene network disrupted by obesity

Mar 17 2008

According to new research an entire network of genes in the body is disrupted by overeating and this not only causes obesity, but also diabetes and heart disease.

The researchers say the discovery may lead to the possibility of predicting which ways obesity will affect a person.

The researchers developed a new method of analyzing DNA and used it to reveal that obesity is complex in ways that had not been previously understood.

Researcher Eric Schadt, executive director of Genetics at Merck Research Laboratories says obesity is not a disease that is the result of a single change to a single gene - it changes entire networks.

Schadt's team identified networks of hundreds of genes that appear to be disrupted when mice were exposed to a high-fat, western-type diet.

When they examined a database of Icelandic people being studied by Decode Genetics Inc they discovered people have the same networks and the discovery led to a joint study.

The two teams from Genetics at Merck Research and Decode Genetic conducted a detailed study of 1,000 blood samples and almost 700 samples of fat tissues from Icelandic volunteers.

The results showed that people who have a higher body mass index, a measurement of obesity, have characteristic patterns of gene activation in their fatty tissues not seen in DNA taken from blood.

The researchers say it illustrates that the common forms of these diseases are very complex and simple genetic tests cannot detect these networks.

The researchers say some people have networks that predispose them to diabetes when they become obese, others to high cholesterol and clogged arteries and some network patterns appeared to predispose some people to metabolic syndrome, in which patients develop a cluster of symptoms including high blood sugar, high blood pressure and clogged arteries.

Schadt says his team now hopes to study these networks and identify the genes most likely to cause the disease which could lead to new drugs designed to target their activity.

The researchers say a good diet and exercise remain the best ways to prevent the onset of obesity.

Schadt says if altering lifestyle is not an option, they can identify which network is going to be most significantly altered and then bring that network into a state that it looks like when you are on a normal diet.

Schadt's team suggest the diseases of obesity appear to originate in the immune system and the network is enriched for genes that are involved in macrophages.

The researchers say in a normal state these things are keeping the body free of infection and fighting off things that want to harm the body and this network is significantly changed by a high-fat diet.

The research is published in the journal Nature.