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

  • Shahar Azar
  • Shiri Sherf-Dagan
  • Alina Nemirovski
  • Muriel Webb
  • Asnat Raziel
  • Andrei Keidar
  • David Goitein
  • Nasser Sakran
  • Oren Shibolet
  • Joseph Tam
  • Shira Zelber-Sagi
Original Contributions

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.

Keywords

Endocannabinoids Laparoscopic sleeve gastrectomy Obesity Metabolic parameters 

Notes

Funding Information

This study was supported (in part) by a grant no. 3-10470 from the Chief Scientist’s Office of the Ministry of Health, Israel, to O.S. and a grant from the Israeli Science Foundation (ISF; 617/14) to J.T. The funding source did not play a role in the design, conduct, and analysis of the study or the decision to submit this manuscript for publication.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in this study were approved by the institutional research committees in both participating hospitals and in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was preregistered in the NIH registration website (TRIAL no. NCT01922830).

Statement of Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.Department GastroenterologyTel-Aviv Medical CenterTel-AvivIsrael
  3. 3.Department of NutritionAssuta Medical CenterTel-AvivIsrael
  4. 4.Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael
  5. 5.Assia Medical GroupAssuta Medical CenterTel-AvivIsrael
  6. 6.Department of General Surgery, Assuta Ashdod Public Hospitalaffiliated to the Ben-Gurion UniversityBeer-ShebaIsrael
  7. 7.Department of Surgery CSheba Medical CenterTel HashomerIsrael
  8. 8.Department of Surgery AEmek Medical CenterAfulaIsrael
  9. 9.Rappaport Faculty of MedicineTechnion Israel Institute of TechnologyHaifaIsrael
  10. 10.School of Public Health, Faculty of Social Welfare and Health SciencesUniversity of HaifaHaifaIsrael

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