Systemic Proteomic Alterations in a Rodent Model of Anorexia Nervosa

Anorexia nervosa (AN) is a severe psychiatric disease that results in significant bodyweight loss that can have severe medical consequences. Diagnosis of AN is notoriously difficult due to reliance on patient testimonies, which can be highly unreliable. Therefore, understanding the physiological sequela that occur concurrently with AN may help improve diagnosis and better understand the pathophysiology of AN. Purpose: Evaluate serum proteomic alterations in a rodent model of simulated AN. Hypothesis: We hypothesize AN will result in alterations to the circulating proteome. Methods: Eight-week-old female rats (n=8/group) underwent simulated AN via 50-60% food restriction for 30 days (AN). An additional cohort of healthy rats were age-matched and allowed ad libitum access to food (CON, n=5). Afterwards, rats were euthanized and serum collected for measurement of proteomic signatures. Differentially expressed proteins were determined by a False Discovery Rate (FDR) adjusted p<0.05 and >0.6-fold difference between groups. Results: Overall, there were 10 proteins that had a > 0.6-fold difference between AN and CON and FDR adjusted p<0.05. Proteins included: Glycolipid transfer protein (GLTP), Tumor necrosis factor ligand superfamily member 10 (TNFSF10), Ribonuclease P protein subunit p25 (RPP25), Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1), CD177 antigen (CD177), Matrilin-3 (MATN3), Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4), Ubiquitin-conjugating enzyme E2 D3 (UBE2D3), S-arrestin (SAG), Alpha-synuclein (SNCA). Of the ten differentially expressed proteins, nine were lower in AN compared to CON. One protein (S-arrestin) was higher in AN compared to CON. Conclusion: AN results in systemic alterations to the circulating proteome. Identifying these alterations may provide opportunities to develop biomarkers for the early diagnosis of AN and/or better understand the pathophysiology of AN and associated health complications. This study was supported by NIH Grant K12HD051959 and Beth Israel Deaconess Medical Center Translation Spark Hubs Grant. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.