http://www.efluxmedia.com/news_Studies_Find_Obesity_Is_the_Result_of_Comple
x_Networks_of_Genes_15250.html

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

In two related studies, scientists at Merck Research Laboratories (MRL) and
their collaborators used large-scale analyses of data on DNA variations,
gene expression patterns in disease-relevant tissues and clinical data to
identify molecular networks underlying metabolic disorders.

The first study, involving Merck researchers and colleagues from the
University of California at Los Angeles, used liver and fat tissue samples
from mice to identify genetic variations associated with obesity, diabetes
and atherosclerosis. Then, the authors constructed gene networks and
identified core groups of genes in these networks that caused the diseases.
Based on various analyses, the authors identified and experimentally
validated three novel genes causally related to obesity-associated traits:
Lpl, Pmpll and Lactb. All of them provide new targets for anti obesity
drugs because they seem key players in the genetic network that control
girth.

The second study by researchers from Merck, the Icelandic company deCODE
Genetics and the National University, Iceland involved more than 1,000
people known to be susceptible to obesity and then used a powerful computer
to match data on genetic makeup, gene use and obesity to identify networks
of gene interactions altered in individual susceptible to obesity. A gene
expression network constructed from human fat tissue contained a similar
core group of genes found to be causally related to obesity in the mouse
study.

“What the new methods we’ve developed deliver is the complex web (network)
of interacting genes in disease relevant tissues that actually lead to
disease. These studies strongly support the theory that common diseases
such as obesity result from genetic and environmental disturbances in
entire networks of genes rather than in a handful of genes. If diseases
like obesity are the result of complex networks of genes, the accurate
reconstruction of these networks will be critical to identifying the best
therapeutic targets,” Dr. Eric Schadt, executive director of Genetics at
Merck Research Laboratories and senior author wrote in the studies.

Dr. Schadt also said a good diet and exercise remain the best ways to
prevent the onset of obesity.

"If you are not going to alter your lifestyle, we can identify what network
is going to be most significantly altered. Then we can bring that network
more into a state to where it looks like when you are on a normal diet."

Schadt suggests the diseases of obesity seem to originate in the immune
system and the network is enriched for genes that are involved in
macrophages.

"In a normal state these things are keeping you free of infection and
fighting off things that want to harm your body. This network is also
significantly changed when you are on a high-fat diet," he added.

The results of the studies appeared in the journal Nature.