Attenuation of Anorexia-Like Phenotype Through Obese Adipose Tissue Transplant
Abstract
Anorexia nervosa (AN) is a complex eating disorder primarily affecting women and is characterized by a low body mass index, resulting in death in 10% of cases. AN occurs in approximately 1%-3% of Veterans and active Service Members, and is highly prevalent in those suffering from post-traumatic disorder. Current cognitive treatments focus on normalizing feeding behavior, but are largely ineffective. Furthermore, no approved pharmacological treatments exist for AN. Recent findings from large human genetic studies have revealed that metabolic traits make up a large part of the risk for AN. Novel treatments targeting metabolic factors could improve outcomes in AN. Recently it was found that obese mice fed a high-fat diet show permanent changes to their fat tissue, even after losing weight: an effect termed metabolic memory. Interestingly, our preliminary results show that transplanting fat tissue from obese mice into normal weight recipient mice reduced weight loss in recipients exposed to conditions that induce AN-like symptoms. Specifically, normal mice will rapidly lose weight when food is restricted and they have access to a running wheel. Under these conditions, normal mice exhibit symptoms of AN, in which they exercise excessively on the wheel and do not eat enough to support their bodyweight. Thus, while normal mice rapidly lose weight under these conditions, our preliminary results indicate that normal mice receiving a fat transplant from an obese mouse are protected from weight loss. Our proposal aims to identify the mechanisms underlying this effect to aid the development of highly effective, metabolically based treatment for AN. First, we will identify how transplanting obese fat alters the metabolic and behavioral profile of the recipient mouse to become resistant to developing AN-like symptoms. Second, we will determine whether specific neuronal populations, within a brain structure called the hypothalamus, alter their activity in response to peripheral signals from transplanted fat from obese mice. In summary, we will identify how peripheral signals from fat modify the activity of hypothalamic neurons to regulate metabolism and behavior. Our findings could lead to novel treatments for AN.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210084
Entities
People
- Stephanie Dulawa
Organizations
- United States Army
- University of California, San Diego