MON-714 Bariatric Surgery and Lorcarserin Administration Differentially Affect the Myostatin-Activin-Follistatin-Inhibin Axis: Results from Two Interventional Studies

Abstract Disclosure: V. Gutierrez de Pineres: None. A. Ramirez Cisneros: None. K. Stefanakis: None. G. Anastasiou: None. C. Mantzoros: Abbott Laboratories, Merck, MLSC, Merck, Boehringer Ingelheim, Regeneron Pharmaceuticals, Genfit, Ansh labs, Novo Nordisk, Amgen Inc, Coherus, Laekna, TMIOA, Madrigal, Biodexa, Esperion. The development of weight loss treatments that achieve concomitant fat loss with lean mass preservation would be ideal. Although 25–39% of weight loss induced by anti-obesity medications results from lean mass loss, the short-term effects of bariatric surgery and serotonin 2C (5-HT2C) receptor agonists on hormones regulating muscle and bone have not been fully elucidated. The Myostatin-Activin-Follistatin (MAFI) axis, crucial for maintaining muscle and bone integrity, requires further investigation to clarify its response to weight loss.This study analyzed data from two trials: a six-month, placebo-controlled study in 36 individuals with obesity randomized to receive Lorcarserin 10mg twice daily or placebo (Study 1) and a 12-month long non-randomized, open-label study of 14 patients undergoing Roux-en-Y gastric bypass (RYGB) or laparoscopic gastric banding (LGB) (Study 2). Clinical, anthropometric and MAFI axis components were measured via Enzyme Linked Immunosorbent Assays (ELISAs). Mixed-effects models were fitted for factors visit, treatment, and visit*treatment interaction, adjusting for Follistatin (FST) and Follistatin-like 3 (FSTL-3). Values < 0.00625 were considered significant due to multiple comparisons.In Study 1, Lorcaserin reduced body weight by 7.74% and fat mass by 8.46% (p: 0.03 ) at 6 months without affecting significantly lean mass or bone mass. Circulating Myostatin and the Myostatin/FST ratio tended to increase (p: 0.03, p: 0.01, respectively), whereas Activins and Follistatins remained unchanged. In Study 2, patients who underwent bariatric surgery achieved a more pronounced weight loss of 17.58% at 6 months post-surgery (p:<0.001). Myostatin levels decreased across all post hoc comparisons (p:<0.001) and FSTL-3 levels declined (p: <0.001; respectively). Free and total IGF-1 remained unchanged in both studies.Lorcaserin administration for 6 months, during which patients achieved minor weight loss and improvement in metabolic outcomes, did not significantly affect MAFI axis hormones apart from Myostatin. Bariatric surgery resulted in more significant weight loss and metabolic outcomes and showed notable hormonal shifts in Myostatin and FSTL-3 (all p:<0.006). Further investigation into short and long-term effects of weight loss interventions not only on body weight and metabolic outcomes but also on muscle and bone changes as well as hormones regulating weight and lean mass loss are needed. Presentation: Monday, July 14, 2025