UC San Diego

Anorexia nervosa (AN) is a severe eating disorder that primarily affects young women and girls and is characterized by abnormal restrictive feeding and a dangerously low body-mass index. AN has one of the highest mortality rates of any psychiatric disorder, and no approved pharmacological treatments exist. Current psychological and behavioral treatments are largely ineffective, and relapse is common. Relatively little basic research has examined biological mechanisms that underlie AN compared to other major neuropsychiatric disorders. A recent large-scale genome-wide association study (GWAS) revealed that the genetic architecture of AN has strong metabolic as well as psychiatric origins, suggesting that AN should be reconceptualized as a metabo-psychiatric disorder. Therefore, identifying the metabo-psychiatric mechanisms that contribute to AN may be essential for developing effective treatments. Activity-based anorexia (ABA), which refers to the weight loss, hypophagia, and hyperactivity exhibited by rodents exposed to both running wheels and scheduled fasting, provides a model for aspects of AN. Therefore, more work is required to understand how traditionally viewed distinct pathways for metabolic regulation vs. psychiatric phenotypes interact to produce AN-like phenotypes. In the periphery, adipose tissue has been found to retain metabolic memory in body weight regulation and has been implicated in AN etiology. In this study, we showed that transplanting white adipose tissue from high-fat fed (HFD) obese mice into normal-weight recipient mice protected against weight loss induced by the ABA paradigm. Our result supports the utility of ABA in study the metabo-psychiatic origins of AN, encourages further work to further uncover metabolic processes that regulate ABA to ultimately identify novel treatment strategies for AN.