More and more people throughout the world suffer from obesity.
Currently about 500 million people are obese, including about 15 million
The causes of obesity are often an unhealthy diet, too
little physical activity and a genetic predisposition. In particular,
people with an altered obesity risk gene called FTO (FTO is the
abbreviation for "fat mass and obesity-associate) are more often obese.
‘People in whom the FTO gene and variants of the dopamine D2 receptor gene are altered have a higher risk of developing obesity and diabetes.’
Signals from the brain
play an important role in the development of obesity and diabetes. Here an important neurotransmitter is dopamine.
DZD scientists from Tübingen and Munich, together with Swedish and
American colleagues, have investigated how mutations in the obesity risk
gene FTO and variants of the dopamine D2 receptor gene interact. Their
results suggest that people in whom both genes are altered have a higher
risk of developing obesity and diabetes.
But how do the gene variants work? Why can they cause people to
"FTO is strongly expressed in the central nervous
system," said PD Dr. Martin Heni of the Institute for Diabetes Research
and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the
University of Tübingen. "Studies on rodents show that altered FTO
influences dopamine signaling in the brain and thus leads to higher food
The "reward hormone" dopamine plays an important role in the
regulation of appetite. If the information that you have already eaten
is not transmitted correctly, then your desire for food increases. One
of the causes for this may be an insufficient number of dopamine D2
receptors to which the neurotransmitter binds.
Researchers of the German Center for Diabetes Research have now
investigated the effects when both the FTO gene and the gene for the
dopamine D2 receptor, ANKK1/Taq1A, are mutated. For this purpose, they
examined samples from the Tübingen Family Study (n = 2245) and the Malmo
Diet and Cancer Study (n = 2921). They found that about 20 percent of
the participants were carriers of both mutations.
"Our studies show that when both genes are mutated, this can have
a far-reaching effect on health. If due to the ANKK1 polymorphism there
are fewer dopamine D2 receptors, those affected with mutated FTO have a
higher percentage of body fat, more abdominal fat and low sensitivity
to insulin in the body. In addition, in the caudate nucleus, the brain
region that is important for dopamine metabolism, insulin sensitivity
was altered," said Heni, summarizing the results.
"From this we conclude
that the effects of a mutated FTO gene depend on the number of dopamine
D2 receptors," added his IDM colleague Professor Hubert Preissl. If an
affected individual is a carrier of both mutated genes, his or her risk
of diabetes and obesity is increased. "Unfortunately, this unfavorable
combination of both gene mutations is present in about one-fifth of the
population," said Heni.
The findings suggest that FTO influences dopamine signaling not
only in rodents, but also in humans. This interaction not only appears
to be important for body weight, but also for the metabolism in the
entire body. FTO gene mutations are important risk factors for
overweight and diabetes. However, the effects are less critical if there
are sufficient dopamine D2 receptors.