期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 315, 期 4, 页码 E489-E495出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00355.2017
关键词
anandamide; 2-arachidonylglycerol; inflammation tight-junction proteins; intestinal fat sensors; n-acylethanolamines
资金
- National Health and Medical Research Council (NHMRC) Career Development Fellowship [1022706]
- NHMRC Senior Research Fellowship [1103020]
- Royal Adelaide Hospital Research Committee Clinical Project Grant
- National Institutes of Health [DA-034009, DK114978]
- NATIONAL INSTITUTE ON DRUG ABUSE [R00DA034009] Funding Source: NIH RePORTER
Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in highfat 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 1) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG), and OEA in humans; and 2) examine relationships to intestinal permeability, inflammation markers, and incretin hormone secretion. Twenty 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), tumor necrosis factor-alpha (TNF alpha), 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) (by RT-PCR) were assessed. Fasting plasma AEA was increased in obese compared with lean and overweight patients (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 compared with lean and overweight subjects. The relationships between plasma AEA with duodenal ZO-1, IAP, and GIP suggest that altered endocannabinoid signaling may contribute to changes in intestinal permeability, inflammation, and incretin release in human obesity.
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