Muscular Proteomic Alterations During Simulated Anorexia Nervosa Are Not Resolved Following Weight Recovery

Anorexia nervosa (AN) is associated with significant bodyweight loss as well as muscle atrophy. However, little is known regarding cellular mechanisms altered in skeletal muscle during the low-weight phase status of the disease nor following weight recovery. PURPOSE: Evaluate proteomic alterations within skeletal muscle of rats during simulated AN and following weight recovery. METHODS: Rats (n = 8) underwent simulated AN via 50-60% food restriction for 30 days (AN). Another cohort of rats underwent simulated AN for 30 days, afterwards rats were provided food ad libitum for an additional 30 day to elicit weight recovery (AN-Rec, n = 8). A final cohort of healthy rats were allowed ad libitum access to food throughout interventions (CON, n = 8). Following designated interventions, gastrocnemius muscle was harvested and analyzed for proteomic signatures. Differentially expressed proteins underwent False Discovery Rate correction. Significantly differentially expressed proteins were defined as having adjusted p < 0.05 and > 0.6-fold difference in protein content between groups. After identification of differentially expressed proteins, protein pathway analysis was completed with the KEGG database. RESULTS: Gastrocnemius muscle mass was ~32% lower in AN compared to CON, which remained ~12% lower in AN-Rec compared to CON. Over 250 proteins were differentially expressed between groups. The top five differentially regulated pathways included neomycin, kanamycin and gentamicin biosynthesis; proximal tubule bicarbonate reclamation; starch and sucrose metabolism; pentose phosphate pathway; and galactose metabolism. Of the proteins that were altered during AN, many did not recover with weight recovery (AN-Rec). CONCLUSION: AN results in profound changes to the skeletal muscle proteome; many such alterations are not restored following weight recovery. These results suggest AN induces long-term deterioration to skeletal muscle health. Supported by: This study was supported by NIH Grant K12HD051959 and Beth Israel Deaconess Medical Center Translation Spark Hubs Grant.