Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion

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dc.contributor.authorLittle, T.J.
dc.contributor.authorCvijanovic, N.
dc.contributor.authorDiPatrizio, N.V.
dc.contributor.authorArgueta, D.A.
dc.contributor.authorRayner, C.K.
dc.contributor.authorFeinle-Bisset, C.
dc.contributor.authorYoung, R.L.
dc.date.issued2018
dc.descriptionFirst published February 13, 2018
dc.description.abstractIntestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion.20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed.Fasting plasma AEA was increased in obese, compared with lean and overweight (P<0.05), with no effect of BMI group or ID lipid infusion on plasma 2-AG or OEA. Duodenal expression of IAP and ZO-1 was reduced in obese, compared with lean (P<0.05), and these levels related negatively to plasma AEA (P<0.05). The iAUC for AEA was positively related to iAUC GIP (r=0.384, P=0.005).Obese individuals have increased plasma AEA and decreased duodenal expression of ZO-1 and IAP, in comparison to lean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.
dc.description.statementofresponsibilityTanya J. Little, Nada Cvijanovic, Nicholas V. DiPatrizio, Donovan A. Argueta, Christopher K. Rayner, X Christine Feinle-Bisset, and Richard L. Young
dc.identifier.citationAmerican Journal of Physiology - Endocrinology and Metabolism, 2018; 315(4):E489-E495
dc.identifier.doi10.1152/ajpendo.00355.2017
dc.identifier.issn0193-1849
dc.identifier.issn1522-1555
dc.identifier.orcidLittle, T.J. [0000-0001-9814-1036]
dc.identifier.orcidRayner, C.K. [0000-0002-5527-256X]
dc.identifier.orcidFeinle-Bisset, C. [0000-0001-6848-0125]
dc.identifier.orcidYoung, R.L. [0000-0001-5116-4951] [0009-0004-8274-9863]
dc.identifier.urihttp://hdl.handle.net/2440/129868
dc.language.isoen
dc.publisherAmerican Physiological Society
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1022706
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1103020
dc.rights© 2018 the American Physiological Society
dc.source.urihttps://doi.org/10.1152/ajpendo.00355.2017
dc.subjectanandamide
dc.subject2-arachidonylglycerol
dc.subjectinflammation tight-junction proteins
dc.subjectIntestinal fat sensors
dc.subjectn-acylethanolamines
dc.titlePlasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion
dc.typeJournal article
pubs.publication-statusPublished

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