Scimex: A genetic mutation associated with an increased risk of developing eating disorders in humans has now been found to cause several behavioral abnormalities in mice that are similar to those seen in people with anorexia nervosa. The findings, published online April 9 inCell Reports, may point to novel treatments to reverse behavioral problems associated with disordered eating.
been known for a long time that about 50% to 70% of the risk of getting
an eating disorder was inherited, but the identity of the genes that
mediate this risk is unknown," explains senior author Michael Lutter,
MD, PhD, a neuroscientist at the University of Iowa's Carver College of
In earlier studies, Lutter and his team sequenced the
genomes of two large families with multiple members affected by eating
disorders, and they found that family members with eating disorders
often had rare mutations in the estrogen-related receptor alpha (ESRRA)
gene or another gene that influences ESRRA's expression. Both mutations
decreased the activity of the protein expressed by ESRRA. Although the
protein is known to be expressed in the brain, relatively little is
known about its function in neurons.
Through studies conducted in
mice, the researchers now show that levels of ESRRA protein in the brain
are regulated by energy reserves. Also, mice that were genetically bred
to lack the protein exhibited obsessive-compulsive-like behaviors and
social impairments, as well as a decreased willingness to work for
high-fat food when hungry.
"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 'non-genetic' risk. We know that the
rate of eating disorders has been increasing over the past several
decades and this is likely due to social factors, not genetics."
and his colleagues now plan to study the mechanisms involved in
estrogen-related receptor alpha's effects on the brain and to test
whether novel treatments can reverse the behavioral problems seen in
their mouse model.