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Dr. Michael Lutter et al., advance understanding of gene linked to eating disorders

Dr. Michael Lutter, Assistant Professor in the Department of Psychiatry in the Carver College of Medicine and a member of the Obesity Research and Education Initiative, and a team of researchers at the University of Iowa recently published an article in Cell Reports (PDF icon) entitled "Behavioral Disturbances in Estrogen-Related Receptor alpha-Null Mice." Building on their discovery of a gene linked to eating disorders in humans, the team has 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. 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.

Through a series of experiments with genetically engineered mice, Lutter and his team showed that mice without the ESRRA gene have behavioral abnormalities related to eating and social behavior. The mice also exhibited impaired social interaction and female mice without the gene show increased compulsive grooming, which may mimic obsessive-compulsive-type behavior 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 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. These new findings may point to particular neural circuits that could be targets to treat abnormal behaviors associated with eating disorders.

Thursday, April 16, 2015