Gene Linking Stress to Obesity & Diabetes

Gene Linking Stress to Obesity & Diabetes Discovered

Changes in the activity of a single gene in the brain can lead to metabolic changes that cause mice to develop symptoms associated with type 2 diabetes, as well as trigger anxious behavior.

These findings, discovered by Weizmann Institute of Science researchers, were published online this week in the Proceedings of the National Academy of Sciences (PNAS).

The constant stress many are exposed to in our modern society may thus be taking a heavy toll: Anxiety disorders and depression, as well as metabolic disorders such as obesity, type 2 diabetes and arteriosclerosis, have all been linked to stress.

These problems are reaching epidemic proportions. Type 2 diabetes alone is expected to affect some 360 million people around the world in 20 years.

The connection between stress, changes in appetite and anxiety-related behavior was recently proven scientifically, but the exact reasons for this were not clear until Dr. Alon Chen of the Rehovot institute’s neurobiology department and colleagues made their gene discovery.

They found that all the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes in the metabolism of various substances and even changes in food preferences.

The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved in tying all of these together. Produced in certain brain cells – especially in times of stress – it is known to play a role in regulating the body’s stress response.

These nerve cells have extensions that act as “highways” to speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions – oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including anxiety levels.

Nerve cells in both these areas have special receptors for Ucn3 on their surfaces, and the protein binds to these receptors to initiate the stress response.

The researchers developed a new, finely tuned method for influencing the activity of a single gene in one area in the brain, using it to increase the amounts of Ucn3 produced in just that location.

They found that heightened levels of the protein produced two different effects: The mice’s anxiety-related behavior increased, and their bodies also underwent metabolic changes. With excess Ucn3, their bodies burned more sugar and fewer fatty acids, and their metabolic rate sped up.

These mice began to show signs of the first stages of type 2 diabetes: A drop in muscle sensitivity to insulin delayed sugar uptake by the cells, resulting in raised sugar levels in the blood. The pancreas then produced extra insulin to make up for the perceived “deficit.”

“We showed that the actions of single gene in just one part of the brain can have profound effects on the metabolism of the whole body,” says Chen.

This mechanism, which appears to be a “smoking gun” tying stress levels to metabolic disease, might, in the future, point the way toward the treatment or prevention of a number of stress-related diseases.