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

BackgroundThe 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.ObjectivesThis 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.MethodsSixty-five morbidly obese patients (age 42.789.27years; BMI 42.005.01kg/m(2)) underwent laparoscopic sleeve gastrectomy (LSG) surgery, and were followed up for 12months. 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.ResultsLevels 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).ConclusionsThis 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.