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Thromb Haemost 2015; 113(04): 838-850
DOI: 10.1160/TH14-06-0506
Blood Cells, Inflammation and Infection
Schattauer GmbH

Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways

Fabrizio Montecucco   *
1   Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
2   Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
3   Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
,
Sébastien Lenglet   *
1   Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
Alessandra Quercioli
1   Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
Fabienne Burger
1   Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
Aurélien Thomas
4   Unit of Toxicology, CURML, University hospital of Geneva, University of Geneva, Geneva, Switzerland
,
Estelle Lauer
5   Unit of Toxicology, CURML, University hospital of Lausanne, University of Lausanne, Lausanne, Switzerland
,
Analina Raquel da Silva
1   Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
François Mach
1   Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
Nicolas Vuilleumier
2   Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
,
Elisabetta Bobbioni-Harsch
6   Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland
,
Alain Golay
6   Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland
,
Thomas H. Schindler   #
7   Department of Radiology, Division of Nuclear Medicine, Cardiovascular Imaging, Johns Hopkins University, Baltimore, Maryland, USA
,
Zoltan Pataky   #
6   Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

Received: 10 June 2014

Accepted after major revision: 09 October 2014

Publication Date:
24 November 2017 (online)

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Summary

Paradoxically, morbid obesity was suggested to protect from cardiovascular co-morbidities as compared to overweight/obese patients. We hypothesise that this paradox could be inferred to modulation ofthe “endocannabinoid” system on systemic and subcutaneous adipose tissue (SAT) inflammation. We designed a translational project including clinical and in vitro studies at Geneva University Hospital. Morbid obese subjects (n=11) were submitted to gastric bypass surgery (GBS) and followed up for one year (post-GBS). Insulin resistance and circulating and SAT levels of endocannabinoids, adipocytokines and CC chemokines were assessed pre- and post-GBS and compared to a control group of normal and overweight subjects (CTL) (n=20). In vitro cultures with 3T3-L1 adipocytes were used to validate findings from clinical results. Morbid obese subjects had baseline lower insulin sensitivity and higher hs-CRP, leptin, CCL5 and anandamide (AEA) levels as compared to CTL. GBS induced a massive weight and fat mass loss, improved insulin sensitivity and lipid profile, decreased C-reactive protein, leptin, and CCL2 levels. In SAT, increased expression of resistin, CCL2, CCL5 and tumour necrosis factor and reduced MGLL were shown in morbid obese patients pre-GBS when compared to CTL. GBS increased all endocannabinoids and reduced adipocytokines and CC chemokines. In morbid obese SAT, inverse correlations independent of body mass index were shown between palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) levels and inflammatory molecules. In vitro, OEA inhibited CCL2 secretion from adipocytes via ERK1/2 activation. In conclusion, GBS was associated with relevant clinical, metabolic and inflammatory improvements, increasing endocannabinoid levels in SAT. OEA directly reduced CCL2 secretion via ERK1/2 activation in adipocytes.

Keywords

Endocannabinoids - obesity - subcutaneous adipose tissue - chemokine

* These authors contributed equally as first authors.


# These authors contributed equally as last authors.


 

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