Topical Area: Neuroscience/Nutrition and the Brain
Neuroscience/Nutrition and the Brain (Poster Session)
(P27-039-23) Odd-Chain Saturated Fatty Acids Have Acylcarnitine Metabolites That Are Full-Acting Endocannabinoids: Implications for Nutritional Mental Health Support
Stephanie Venn-Watson, DVM, MPH: Seraphina Therapeutics: Executive Role (e.g. Board of Directors) (Ongoing); Ownership Interest (Ongoing); Royalties or Patent Beneficiary (Ongoing); Stock Shareholder (excluding mutual funds) (Ongoing)
Objectives: As an emerging essential fatty acid, pentadecanoic acid (C15:0) has pleiotropic activities relevant to cardiometabolic, liver, heart and immune health. Given the recent discovery of pentadecanoylcarnitine, a key C15:0 metabolite and the second-ever found full acting endocannabinoid, we explored endocannabinoid activities of closely related molecules to better understand new nutrient-based metabolites that may support mental health.
Methods: Standardized cell-based GPCR cAMP assays were used to measure and compare maximum cannabinoid receptor 1 and 2 (CB1 and CB2 receptors, respectively) agonist activities for C15:0 and C17:0 acylcarnitines, as well as C15:0 and C17:0 ethanolamides, across 10 concentrations compared to the positive control, CP55940 (tetrahydrocannabinol, or THC). Half-maximal effective concentrations (EC50) were also determined.
Results: Both C15:0 and C17:0 acylcarnitines were full CB1 and CB2 agonists. Pentadecanoylcarnitine had 98% and 93% maximum CB1 and CB2 agonist responses with an EC50 of 8.1 µM and 6.5 µM, respectively, while heptadecanoylcarnitine had 97% and 91% maximum CB1 and CB2 agonist responses with an EC50 of 8.7 µM and 6.7 µM, respectively. C15:0 ethanolamide was a partial CB1 agonist (46% maximum activity, EC50 5.5 µM), while C17:0 ethanolamide had no endocannabinoid activities.
Conclusions: Here, we report that odd-chain saturated fatty acids (C15:0 and C17:0), which have emerged as healthy and active fats, also have a newly discovered family of full-acting endocannabinoid metabolites to support improved sleep quality, lower anxiety and lower pain. There is a need to evaluate the potential role that population-wide avoidance of all saturated fats, including C15:0 and C17:0, may be having on the coinciding rise in mental health and sleep disorders.
