Disturbed regulation of food intake occurs in several human conditions e.g. obesity, anorexia, cachexia and in children with failure to thrive, collectively referred to as eating disorders. Our research is focused mainly on anorexia, in particular the psychiatric diagnosis anorexia nervosa. Anorexia nervosa is a complex and poorly understood disorder that currently lack effective pharmacological or other biological target-directed therapy. Approximately one out of hundred young women and one out of thousand men are affected by anorexia nervosa. Almost twice as many are affected by bulimia nervosa. In addition, it has been estimated that 10-20% of all women display abnormal eating behavior and/or have a complicated relation to food, without being diagnosed with an eating disorder. Little is known about what causes the disorders, but it has been shown that those that are affected seem to have a hereditary sensitivity to external stimuli that can trigger the disease. In fact, 50-80% of the background of anorexia nervosa is attributed to genetic factors.
Food intake and energy balance are controlled by interactions between the brain, in particular the hypothalamus, often called the feeding center of the brain, and the periphery. The hypothalamus receives signals about energy status from the periphery, such as circulating leptin and insulin levels, and transforms this information to an appropriate response – to eat or not to eat. When this complex signaling system is malfunctioning it can lead to abnormal eating behavior that, in worst case, is fatal.
The overall goal for our group is to understand the development and function of molecular mechanisms involved in hypothalamic regulation of food intake to offer new target molecules to study with regard to regulation of food intake and eating disorders. Such biomarkers may assist in the development of evidence based clinical practice and promote individualized therapy of eating disorders.
Our results so far strongly indicate that anorexia could be caused by hypothalamic mitochondrial dysfunction and over production of reactive oxygen species (ROS). ROS could initially act as a signaling molecule on hypothalamic neurons, leading to decreased food intake, oxidative stress and in the long run inactivation and degeneration of hypothalamic neurons. The question why the hypothalamic neurons are more vulnerable than other neurons, as well as other tissues, remains to be answered. A possible explanation is that some factor(s) make some neurons more sensitive to mitochondrial deficiency, increased levels of ROS and/or oxidative stress.
We have therefore initiated several studies that can contribute to increasing the knowledge concerning hypothalamic regulation of food intake and energy metabolism, and the interaction between inflammation, oxidative stress and these mechanisms. These studies may further change the research regarding food intake regulation and eating disorders from a strictly behavioral/psychological view towards a more neurological/immunological perspective. In the future this will also be of importance for the treatment of these disorders.
Eating disorders & regulation of food intake group publications link to google scholar