New research has shed light on how disruption of a protein called ESRRA, which is linked to eating disorders, affects behavior. ESRRA (an acronym for estrogen-related receptor alpha) is a “transcription factor”— a protein that regulates the way a gene is expressed. The findings may have broad implications for conditions that involve inflexible behaviors and social deficits, both of which are common in people with eating disorders.
Published April 21st in Cell Reports, the research was led by 2008 and 2012 NARSAD Young Investigator grantee Michael L. Lutter, M.D., Ph.D. The team included 2012 NARSAD Young Investigator grantee Huxing Cui, Ph.D.; 2006 and 2008 Young Investigator grantee Jason J. Radley, Ph.D.; and 2007 and 2009 Young Investigator grantee Andrew A. Pieper, M.D., Ph.D.
Mutations to ESRRA, which is expressed in the brain and spinal cord, increase the risk for developing an eating disorder. The researchers found, in mice, that limiting food intake increased ESRRA activity throughout the brain. This suggests that ESRRA is regulated by the body’s energy supply. To understand exactly how ESRRA may affect eating patterns, the researchers looked at the behaviors of mice bred to have inactive ESRRA proteins, and those whose ESRRA was “knocked out”—eliminated through a genetic technique.
Under a restricted diet, both the mice born with inactive ESRRA and the mice with knocked-out ESRRA made less effort to get food. This suggests that loss of ESRRA activity may contribute to the development of eating disorders by blocking people from responding appropriately to inadequate diets (by seeking more food).
ESRRA-deficient female (but not male) mice also engaged in more grooming, a trait believed to reflect a compulsion associated with eating disorders. This difference among the sexes suggests that ESRRA deficiency may have a greater impact on females. The researchers believe this question should be further investigated in relation to other psychiatric disorders that disproportionately affect women, including major depression and anxiety disorders.
Further research, the scientists say, will also need to look at the effects of the precise ESRRA mutation associated with eating disorders.