Circulating Endocannabinoids Are Reduced Following Bariatric Surgery and Associated with Improved Metabolic Homeostasis in Humans

Background: The endocannabinoid (eCB) system plays a key role in the development of obesity and its comorbidities. Limited information exists on the changes in circulating eCBs following bariatric surgery. Objectives: This study aims to (i) assess the circulating levels of eCBs and related molecules and (ii) examine the association between their levels and numerous clinical/metabolic features pre- and post-operatively. Methods: Sixty-five morbidly obese patients (age 42.78 ± 9.27 years; BMI 42.00 ± 5.01 kg/m ² ) underwent laparoscopic sleeve gastrectomy (LSG) surgery, and were followed up for 12 months. Data collected included anthropometrics and metabolic parameters. The serum levels of the eCBs, 2-arachidonoylglycerol (2-AG), anandamide (AEA); and their related molecules, arachidonic acid (AA) and oleoylethanolamine (OEA) were measured by liquid chromatography-mass spectrometry. Results: Levels of 2-AG, AEA, and AA were reduced post operatively with no differences in serum OEA levels. The delta changes in eCB levels between pre- and post-operation were correlated with the delta of different metabolic parameters. Positive correlations were found between delta AA and waist circumference (WC) (r = 0.28, P < 0.05), free fat mass (r = 0.26, P < 0.05), SteatoTest score (r = 0.45, P < 0.05), and ALT (r = 0.32, P < 0.05). Delta AEA levels positively correlated with WC (r = 0.30, P < 0.05). Delta 2-AG levels positively correlated with total cholesterol (r = 0.27, P < 0.05), triglycerides (r = 0.55, P < 0.05), and SteatoTest score (r = 0.27, P < 0.05). Delta OEA levels negatively correlated with fasting glucose levels (r = − 0.27, P < 0.05). Conclusions: This study provides compelling evidence that LSG surgery induces reductions in the circulating 2-AG, AEA, and AA levels, and that these changes are associated with clinical benefits related to the surgery including reduced fat mass, hepatic steatosis, glucose, and improved lipid profile.