UC San Diego

Anorexia Nervosa (AN) is an eating disorder observed primarily in girls and women. AN is characterized by a low body mass index, hypophagia, and hyperactivity. While AN has one of the highest mortality and relapse rates of all psychiatric disorders, there are no approved pharmacological treatments for AN. However, a recent GWAS study revealed eight metabolic gene loci associated with the development of AN, suggesting a metabolic origin of the development of AN. In the clinical setting, weight regain is one crucial aspect of treating AN.In contrast, obesity patients face weight loss resistance. Recent work shows that obesity alters the metabolite profile of most tissues. Such metabolic profile returns to normal upon weight loss for all tissues except adipose tissues. Such an aspect of obesity is attributed to the metabolic memory of adipose tissues. We sought to introduce metabolic memory of obese adipose tissue in Activity-Based Anorexia (ABA), an animal model of AN's hyperactivity and hypophagia aspect, by transplanting adipose tissues into ABA mice. Our previous study found that obese adipose tissue recipients lose body weight slower than control adipose tissue recipients when subjected to the ABA paradigm. We therefore hypothesized that behavioral benefits to adipose tissue transplantation shown in the ABA paradigm stemmed from its communication to the brain. Here, we show that neonatal ablation of Agouti-Related Peptide (AgRP) neurons significantly disrupts the weight loss resistance introduced by obese adipose transplantation in ABA.