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Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion
- Source :
- Little, TJ; Cvijanovic, N; DiPatrizio, NV; Argueta, DA; Rayner, CK; Feinle-Bisset, C; et al.(2018). Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 315(4), E489-E495. doi: 10.1152/ajpendo.00355.2017. UC Riverside: Retrieved from: http://www.escholarship.org/uc/item/63g7s65h
- Publication Year :
- 2018
- Publisher :
- eScholarship, University of California, 2018.
-
Abstract
- Intestinal 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 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-α (TNFα), 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.
- Subjects :
- Male
0301 basic medicine
Physiology
Endocrinology, Diabetes and Metabolism
Gene Expression
Oleic Acids
Overweight
Oleoylethanolamide
chemistry.chemical_compound
0302 clinical medicine
n-acylethanolamines
Glucagon-Like Peptide 1
anandamide
Anandamide
Endocannabinoid system
inflammation tight-junction proteins
Female
lipids (amino acids, peptides, and proteins)
medicine.symptom
Research Article
Adult
medicine.medical_specialty
Duodenum
Polyunsaturated Alkamides
Incretin
030209 endocrinology & metabolism
Inflammation
Arachidonic Acids
Gastric Inhibitory Polypeptide
GPI-Linked Proteins
Incretins
Permeability
Glycerides
03 medical and health sciences
Thinness
Occludin
Physiology (medical)
Internal medicine
medicine
Humans
Secretion
Obesity
intestinal fat sensors
Intestinal permeability
Tumor Necrosis Factor-alpha
business.industry
Alkaline Phosphatase
medicine.disease
Dietary Fats
Toll-Like Receptor 4
030104 developmental biology
Endocrinology
2-arachidonylglycerol
chemistry
Zonula Occludens-1 Protein
business
Endocannabinoids
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Little, TJ; Cvijanovic, N; DiPatrizio, NV; Argueta, DA; Rayner, CK; Feinle-Bisset, C; et al.(2018). Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 315(4), E489-E495. doi: 10.1152/ajpendo.00355.2017. UC Riverside: Retrieved from: http://www.escholarship.org/uc/item/63g7s65h
- Accession number :
- edsair.doi.dedup.....67df5f3cdde70f2321dc2ebb817416ee