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

Fabrizio Montecucco; Sébastien Lenglet; Alessandra Quercioli; Fabienne Burger; Aurélien Thomas; Estelle Lauer; Analina Raquel da Silva; François Mach; Nicolas Vuilleumier; Elisabetta Bobbioni-Harsch; Alain Golay; Thomas H. Schindler; Zoltan Pataky

doi:10.1160/TH14-06-0506

Thrombosis and Haemostasis, Inhaltsverzeichnis

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^*

¹Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland

²Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland

³Department 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^*

¹Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland

,

Alessandra Quercioli

¹Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland

,

Fabienne Burger

¹Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland

,

Aurélien Thomas

⁴Unit of Toxicology, CURML, University hospital of Geneva, University of Geneva, Geneva, Switzerland

,

Estelle Lauer

⁵Unit of Toxicology, CURML, University hospital of Lausanne, University of Lausanne, Lausanne, Switzerland

,

Analina Raquel da Silva

¹Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland

,

François Mach

¹Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, Geneva, Switzerland

,

Nicolas Vuilleumier

²Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland

,

Elisabetta Bobbioni-Harsch

⁶Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland

,

Alain Golay

⁶Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland

,

Thomas H. Schindler^#

⁷Department of Radiology, Division of Nuclear Medicine, Cardiovascular Imaging, Johns Hopkins University, Baltimore, Maryland, USA

,

Zoltan Pataky^#

⁶Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland

› Institutsangaben

Abstract

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

Volltext

Referenzen

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