TRAIL: A potential new biomarker for muscle health in anorexia nervosa

Concurrent with fat loss, anorexia nervosa (AN) results in significant losses to muscle size and strength, reducing functional capacity and overall quality of life. Biomarkers of muscle health in this population both during active AN and following weight gain are lacking and assessments of muscle size or strength are not often practical. The purpose of this series of experiments was to assess possible biomarkers of muscle health using a rodent model of AN and weight recovery following AN. Methods: Experiment 1: Female Sprague Dawley rats (8 weeks old, n=9) underwent simulated AN for 30 days. Gastrocnemius muscle was then harvested and analyzed for transcriptomic signatures. Data were compared to age-matched healthy control rats (n=9). Experiment 2: Cohorts of female Sprague Dawley rats underwent simulated AN as in Experiment 1. Then an additional cohort of rats underwent weight recovery with 30 days of ad libitum food consumption. AN and AN recovered rats were compared to healthy controls (n=8/group). Following designated interventions (either AN, AN and recovery or ad libitum food consumption), gastrocnemius muscle and serum were collected and underwent proteomics analysis using SOMAscan discovery proteomics. For both experiments, volitional muscle strength was assessed via rear paw grip strength. Results: In experiment 1, TRAIL (TNF-related apoptosis-inducing ligand, Tnfsf10) arose as a significantly altered gene (~52% lower in AN v. CON, p=0.003). Moreover, TRAIL mRNA levels correlated with gastrocnemius mass (r = 0.733, p=0.001) and rear paw grip strength (r = 0.756, p=0.004). In experiment 2, TRAIL protein content between muscle and serum was significantly correlated (r = 0.642, p=0.001). Moreover, TRAIL content in the serum also correlated with gastrocnemius mass (r = 0.833, p< 0.001) and rear paw grip strength (r =0.837, p< 0.001). Conclusion: TRAIL may represent a novel serologic biomarker of muscle health. While TRAIL has previously been categorized as an anti-tumor and apoptosis protein, it may have broader roles in muscle physiology. Future research should validate these findings in humans and attempt to more fully understand TRAIL’s role in muscle physiology. Acknowledgements: This study was supported by the Beth Israel Deaconess Medical Center Translational Spark Hubs Grant, (M.E.R/C.M./L.B.), NIH grant K12HD051959 (M.E.R.) and the Arkansas Integrative Metabolic Research Center Pilot Grant (M.E.R.) as part of the AIMRC Center for Biomedical Research Excellence (COBRE) grant (5P20GM139768). This abstract was presented at the American Physiology Summit 2026 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.