Shahar Azar1, Shiri Sherf-Dagan2,3,4, Alina Nemirovski1, Muriel Webb2, Asnat Raziel5, Andrei Keidar6, David Goitein4,5,7, Nasser Sakran5,8,9, Oren Shibolet2,4, Joseph Tam10, Shira Zelber-Sagi11,12. 1. Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. 2. Department Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel. 3. Department of Nutrition, Assuta Medical Center, Tel-Aviv, Israel. 4. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5. Assia Medical Group, Assuta Medical Center, Tel-Aviv, Israel. 6. Department of General Surgery, Assuta Ashdod Public Hospital, affiliated to the Ben-Gurion University, Beer-Sheba, Israel. 7. Department of Surgery C, Sheba Medical Center, Tel Hashomer, Israel. 8. Department of Surgery A, Emek Medical Center, Afula, Israel. 9. Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel. 10. Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. yossit@ekmd.huji.ac.il. 11. Department Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel. zelbersagi@bezeqint.net. 12. School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel. zelbersagi@bezeqint.net.
Abstract
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/m2) 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.
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 obesepatients (age 42.78 ± 9.27 years; BMI 42.00 ± 5.01 kg/m2) 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.
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