Does genetics affect weight

Gene: the real fatteners?

The genetic causes of obesity are clarified

Who gets fat and who stays thin? Marburg researchers are investigating this question by examining the genetic make-up. They found gene mutations that cause body weight to increase dramatically. It is difficult to fight back.
"I eat very little. Obesity runs in the family for us." - Excuse? Or is there any truth to the story of the genes that make you fat? "About 60 percent of the genetic make-up is responsible for someone becoming overweight," replies Professor Johannes Hebebrand from the University of Marburg. Several genes that affect weight are already known. Some cause obesity, others keep you thin. "Genetic factors can often play a decisive role, especially in people who have severe weight problems as a child," said Hebebrand. With the support of the Federal Ministry of Education and Research (BMBF), he and his staff research known factors and are looking for new ones. The scientists are currently particularly interested in some mutations in the MC4R gene. About two percent of people who are extremely overweight show such mutations. The MC4R gene provides the blueprint for the melanocortin-4 receptor (MC4R). This receptor is found primarily in the hypothalamus, a structure of the brain. It influences the energy balance of the organism and regulates body weight. The researchers know pretty well how many additional kilograms are due to the changes in the MC4R gene: a six-foot-tall male with a mutation weighs on average 13 kg more than other men; a 1.70 meter tall woman even 27 kg more than other women. Affected people tend to be overweight because they are more hungry and at the same time may burn fewer calories than others. This can be explained in terms of molecular biology as follows: If the MC4 receptor is activated, the appetite decreases; activity and energy consumption increase at the same time. Due to the mutations in the MC4R gene, the body produces too few, incorrectly composed or no receptors at all. As a result, the receptors cannot be activated or not fully activated. The result: appetite increases and you consume less energy. But there are not only MC4R gene variants that make you fat: The scientists have now clarified the meaning of the I103 mutation in the same gene. It helps you stay thin. People with this mutation weigh an average of 1.6 kg less than their fellow human beings at a height of 1.80 meters. Your risk of becoming overweight is reduced by 30 to 40 percent. Hebebrand assumes that I103, in contrast to the other MC4R gene mutations, increases the activity of the receptors.

Lose weight only with an iron discipline
The importance of the MC4R gene and some other genes for weight regulation has largely been deciphered. Hebebrand emphasizes, however, that in addition to environmental factors, a whole range of other hereditary factors must play a role. Hebebrand is convinced: "Weight is not standardized in humans. As with height, there is a considerable range. Our genes are largely responsible for this." He regrets that these connections are neglected in the public discussion and that some therapists who care for overweight people are also unknown. It is too seldom acknowledged that severely overweight people can hardly manage to become significantly thinner in the long term because of their genetic predisposition. If you want to lose weight in the long term despite your genetic makeup, iron discipline is required - with regard to diet and physical activity. Anyone who is not told this clearly is quickly discouraged. One consequence is frustrating starvation diets, which often even increase the weight. Hebebrand: "We shouldn't arouse hopes that cannot be fulfilled. It is more important that even very overweight people learn to accept themselves."

Obesity as an evolutionary advantage
For the longest time in history, people who were able to gain weight quickly because of their genetic makeup actually had an advantage. Because those who built up sufficient fat reserves in good times also survived periods of hunger. This advantage is reversed in the industrialized nations: modern lifestyles and eating habits favor obesity, and at the same time periods of hunger no longer occur. Therefore, people with the corresponding hereditary predisposition often put on extreme weight. Obesity is a crucial risk factor for cardiovascular diseases, diabetes and other lifestyle diseases.

Contact Person:
Professor Dr. Johannes Hebebrand
Clinical research group
Clinic for Psychiatry and Psychotherapy
of childhood and adolescence
Philipps University of Marburg
Hans-Sachs-Strasse 4-8
35033 Marburg
Tel .: 06421/2 86 64 66
Fax: 06421/2 86 30 56
Email: [email protected]