1907-LB: A Novel Omega Fatty Acid-Based Exercise Mimetic Targeting AMPKα and PPARδ for Metabolic Health—A Safer Alternative to Synthetic Agonists

Introduction and Objective: Sedentary lifestyles and poor diets contribute to rising metabolic disorders, impacting muscle health. While exercise supports lipid metabolism, many face barriers to regular activity. This study develops an omega fatty acid-based supplement to mimic exercise by activating PPARδ and AMPKα, offering a safer alternative to conventional PPARδ agonists without adverse effects. Methods: C2C12 mouse myoblasts were cultured in DMEM supplemented with 10% FBS and differentiated using 1% horse serum. Fatty acids were conjugated to BSA and applied to myotubes. RNA extraction and qRT-PCR were performed using TaqMan assays, while protein expression was analyzed via Western blot. Mitochondrial function was assessed using JC-1 staining. ROS levels were measured with DCFDA. Flow cytometry was conducted to analyze metabolic markers. Statistical analysis was performed using GraphPad Prism, with significance set at p<0.05. Results: The supplement's efficacy was evaluated in vitro and in vivo. Treated C2C12 myotubes showed significant upregulation of PPARδ and AMPKα, comparable to GW1516 and AICAR, leading to increased expression of CD36, FASN, mCPT1, PRKAA2, and SREBP, which regulate fatty acid uptake, synthesis, and oxidation. In rats, four weeks of supplementation reduced blood triglycerides without affecting body weight or glucose levels. Muscle tissue analysis confirmed elevated PPARδ, HSL, UCP3, and AMPKα, indicating enhanced metabolic activation. Conclusion: The omega fatty acid supplement enhances muscle metabolism by promoting lipid utilization and energy production. Next, its effects on muscle enhancement under resistance exercise will be tested. If successful, it could serve as a safer, natural alternative to traditional exercise mimetics, benefiting those with limited physical activity. Disclosure F. Alrashed: None. H. AlSaeed: None. R. Ahmad: None. Funding This work is supported by the University of Sharja women in Research (120143)