517-P: Postprandial Circulating Endocannabinoidome Mediators—Impact of Host's Metabolic Health and Dietary Fatty Acid Profile

Introduction & Objective: Food digestion and the activity of the gut microbiota enable the production of several nutrient-derived bioactive metabolites. Notably, lipids can be metabolized into endocannabinoidome (eCBome) mediators, a large family of endocannabinoid and their congeners such as N-acyl-ethanolamines (NAEs) and 2-monoacyl-glycerols (2-MAGs) involved in numerous aspects of energy homeostasis. Our objective is to decipher the short-term and postprandial kinetics of dietary fatty acid incorporation into circulating eCBome mediators in individuals living with visceral obesity and type 2 diabetes (T2D).

Methods: The METAc trial consists of a fixed sequence of standardized meals divided in three periods: a) a 3-day run-in control diet, b) a 2-day UFA-rich diet, and c) a 2-day SFA-rich diet. Fasting and postprandial (45-480 min) circulating levels of NAEs and 2-MAGs were measured by LC-MS/MS and analyzed using longitudinal mixed linear models.

Results: Men and postmenopausal women aged 45 to 65 (n=51) were recruited into the following groups: lean, visceral obesity and T2D. Circulating levels of 2-MAGs derived from oleic acid and omega‑3 PUFAs were increased following the 2-day UFA-rich diet (+25 to 120%). Interestingly, circulating levels of all 2-MAGs were rapidly increased along with digestion (+40 to 220%). In contrast, circulating levels of NAEs were decreased throughout the postprandial periods (−40 to 80%). The magnitude of the postprandial response of most NAE and 2-MAG congeners was influenced by the fatty acid profile of the previous meal. In addition, the eCBome profile was impacted by the obesity and T2D status of the host.

Conclusion: This study supports the hypothesis that dietary lipids are rapidly metabolized and incorporated into circulating 2-MAGs. Dietary lipid intake, obesity and diabetes status as well as gut microbiota activity emerge as crucial regulators of the fasting and postprandial circulating eCBome tone.