Washington: Loss of a gene may be responsible for several behavioural changes seen in people with eating disorders, a new study on mice suggests.
Researchers found that mice that lack the estrogen-related receptor alpha (ESRRA) gene are less motivated to seek out high-fat food when they are hungry and have abnormal social interactions.
The effect was stronger in female mice, which also showed increased obsessive-compulsive-like behaviours.
The study also shows that ESRRA levels are controlled by energy status in the mice. Restricting calorie intake to 60 per cent of normal over several days significantly increased levels of ESRRA in the brains of 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," said Michael Lutter, assistant professor of psychiatry at the University of Iowa.
Anorexia nervosa and bulimia nervosa are common and severe mental illnesses. Lutter notes that although 50 to 70 per cent of the risk of getting an eating disorder is inherited, identifying the genes that mediate this risk has proven difficult.
ESRRA is a transcription factor - a gene that turns on other genes. Lutter and his colleagues previously found that a mutation that reduces ESRRA activity is associated with an increased risk for eating disorders in human patients.
In the new study, published in the journal Cell Reports, Lutter's team manipulated ESRRA in mice to investigate the gene's role in behaviour.
"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 said.
"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 added.
Through a series of experiments with genetically engineered mice, Lutter and his team showed that mice without the ESRRA gene have behavioural abnormalities related to eating and social behaviour.
In particular, mice without ESRRA show reduced effort to work for high-fat food when they are hungry. The mice also exhibited impaired social interaction and female mice without the gene show increased compulsive grooming, which may mimic obsessive-compulsive-type behaviour in humans.
In order to refine their understanding of the effects of ESRRA in the brain, the researchers selectively removed the gene from particular brain regions that have been associated with eating disorders.
They found that removing the gene from the orbitofrontal cortex was associated with increased obsessive-compulsive-type behaviours 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.
