Could a Missing Gene Contribute To Eating Disorder Symptoms?
Could a missing gene be responsible for eating disorders? A new animal study suggests that may be the case, as researchers have shown that mice who were missing a specific gene began to show numerous strange behaviors that resemble behaviors seen in humans with anorexia nervosa.
The team, led by Michael Lutter, assistant professor of psychiatry in the UI Carver College of Medicine, found that mice who lacked the estrogen-related receptor alpha (ASRRA) gene show less motivation to seek out high-fat food when they are hungry and exhibit abnormal social interactions.
Interestingly, the effects were strongest in female mice, which also showed signs of obsessive-compulsive behaviors.
The findings, published in Cell Press, also showed that ESRRA levels are regulated by energy status in the mice. By restricting calorie intake to 60 percent of normal over several days, the researchers were able to greatly increase the levels of ESRRA in the brains of otherwise normal mice.
“Decreased calorie intake usually motivates animals, including humans, to seek out high-calorie food. These findings suggest that loss of ESRRA activity may disrupt that response,” Lutter says.
Researchers have believed in a genetic root for eating disorders for years, as 50 to 70 percent of the risk of an eating disorder is inherited, but identifying the specific genes that help mediate this risk has been more difficult than expected.
Researchers describe ESRRA as a “transcription factor” or a gene that serves to turn on other genes. Previous research by Lutter and his team found a mutation which reduces ESRRA is associated with increased risk for eating disorders. ESRRA is commonly expressed in many brain regions which are significantly affected by anorexia, but almost nothing else was known about its function until recently.
“This work identifies estrogen-related receptor alpha as one of the genes that is likely to contribute to the risk of getting anorexia nervosa or bulimia nervosa,” Lutter says. “Clearly social factors, particularly the western ideal of thinness, contribute the remaining ‘nongenetic’ risk, and the increasing rate of eating disorders over the past several decades is likely due to social factors, not genetics,” he adds.
To study the effects of ESRRA, Lutter and his colleagues selectively removed the gene from specific brain regions that have been associated with eating disorders. After, they saw that removing the gene from the orbitofrontal cortex was associated with increased obsessive-compulsive-type behaviors in female mice, while loss of ESRRA from the prefrontal cortex produced mice that were less willing to work to get high-fat food when they were hungry.
The findings lead the researchers to believe particular neural circuits could potentially serve as targets for treating abnormal behaviors associated with eating disorders.
“Mouse models of human neuropsychiatric illnesses are useful for identifying cellular and molecular abnormalities that might contribute to illnesses like eating disorders,” Lutter says. “They are also useful for screening new medications. We plan to start testing novel treatments for anorexia nervosa to see if they reverse behavioral problems in our mice.”