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

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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.

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Funding

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.

Author information

Author notes

  1. Shahar Azar and Shiri Sherf-Dagan contributed equally to this work.

Authors and Affiliations

  1. Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

    Shahar Azar, Alina Nemirovski & Joseph Tam

  2. Department Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel

    Shiri Sherf-Dagan, Muriel Webb, Oren Shibolet & Shira Zelber-Sagi

  3. Department of Nutrition, Assuta Medical Center, Tel-Aviv, Israel

    Shiri Sherf-Dagan

  4. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Shiri Sherf-Dagan, David Goitein & Oren Shibolet

  5. Assia Medical Group, Assuta Medical Center, Tel-Aviv, Israel

    Asnat Raziel, David Goitein & Nasser Sakran

  6. Department of General Surgery, Assuta Ashdod Public Hospital, affiliated to the Ben-Gurion University, Beer-Sheba, Israel

    Andrei Keidar

  7. Department of Surgery C, Sheba Medical Center, Tel Hashomer, Israel

    David Goitein

  8. Department of Surgery A, Emek Medical Center, Afula, Israel

    Nasser Sakran

  9. Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel

    Nasser Sakran

  10. School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel

    Shira Zelber-Sagi

Authors
  1. Shahar Azar
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  2. Shiri Sherf-Dagan
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  3. Alina Nemirovski
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  4. Muriel Webb
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  8. Nasser Sakran
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  9. Oren Shibolet
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  10. Joseph Tam
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  11. Shira Zelber-Sagi
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Corresponding authors

Correspondence to Joseph Tam or Shira Zelber-Sagi.

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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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Azar, S., Sherf-Dagan, S., Nemirovski, A. et al. Circulating Endocannabinoids Are Reduced Following Bariatric Surgery and Associated with Improved Metabolic Homeostasis in Humans. OBES SURG 29, 268–276 (2019). https://doi.org/10.1007/s11695-018-3517-0

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  • DOI: https://doi.org/10.1007/s11695-018-3517-0

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