WIKIMEDIA, GEORGE SHUKLIN
Mice missing the estrogen-related receptor alpha (ESRRA) gene, which has been linked to human eating disorders, weigh 15 percent less than wild-type mice, eat less, and exhibit compulsive behavior, according to a study published today (April 9) in Cell Reports.
Researchers from the University of Iowa’s Carver College of Medicine had previously sequenced the genomes of two human families with a high prevalence of eating disorders and identified rare mutations that led to lower levels of ESRRA, a transcription factor required for making energy-producing mitochondria in the brain. To understand the potential effect of altered ESRRA levels, the scientists examined the brains and behaviors of mice that lack the gene entirely.
In their latest study, the researchers found that mice without ESRRA met the clinical definition of anorexia nervosa, weighing only 85 percent or less of the wild-type weight. When the calories provided to wild-type and mutant mice were restricted, the wild-type mice displayed elevated levels of ESRRA in the brain and put great effort into pressing a lever that provided high-fat food. By contrast, the ESRRA-null mice pressed the same lever less often and received less food than their wild-type littermates. Female mice missing ESRRA also displayed other behavioral disorders, including compulsive grooming or marble burying and difficulty adapting to new situations. These behaviors, which were not observed in male mice without ESRRA, could be important for understanding sex-based differences in mental illness, the authors wrote in their paper.
“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,” study coauthor Michael Lutter of Iowa said in a statement. Although the results may help to explain the 50 percent to 70 percent of eating disorder risk that is genetic, “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” he added.