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

Article Article scientifique Article Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways eng 2015 author Montecucco Fabrizio 651324 author Lenglet Sébastien 589285 author Quercioli Alessandra 688235 author Burger Fabienne 97461 author Thomas Alexandre 523873 author Lauer Estelle 686254 author Da Silva Analina Raquel 814213 author Mach François 27365 author Vuilleumier Nicolas 61406 author Harsch-Bobbioni Elisabetta 26455 author Golay Alain 27404 author Schindler Thomas 662511 author Pataky Zoltan 0000-0002-8720-3833 105295 838-850 10.1160/TH14-06-0506 25413674 0340-6245 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 of the "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. Dewey 576 Dewey 613 Dewey 616 Dewey 614.1 136 Département de biologie structurale et bioinformatique 21E 56 Département de médecine 221 67 Institut de médecine légale 22A2 false 211 Auto-immunité, inflammation et athérosclérose 270 334 Education thérapeutique du patient, diabète et obésité 600 325 Athérosclérose 591 Thrombosis and haemostasis 113 4 3ef26c1b-9d6e-4548-a189-10f1e4691dae Article (Published version) Restricted Gastric.pdf 589454 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de biologie structurale et bioinformatique Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine légale

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Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways	Thrombosis and haemostasis			2015	798	0

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Thomas, Alexandre