Abstract
PurposeTo determine the small intestinal concentration of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their precursors N-acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status.MethodsAn observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18–70 years, BMI 17–40 kg/m2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries.ResultsRegarding ECs, N-arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72–17.6 µg/mL in ileal fluids and 0.014–0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3–71.5 µg/mL in ileal fluids and 0.19–1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein.ConclusionWe quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa.Clinical trial registry number and websiteNCT04143139; www.clinicaltrials.gov.
Highlights
Endocannabinoids (ECs) and their structural congeners N-acylethanolamines (NAEs), known as “endocannabinoid-like molecules”, are endogenous lipid mediators involved in a wide range of biological pathways regulating appetite, nutrient metabolism, energy balance and inflammation [1, 2]
While ECs are acknowledged key mediators in the interplay between gut, microbiota and metabolic health, to the best of our knowledge, their levels and those of NAEs and NAPEs in the gastro-intestinal tract are largely unknown with only one recent human study reporting fecal concentration for single NAPE [51]
For the first time, the concentrations of ECs, NAEs and NAPEs within the gastro-intestinal tract (GIT) are measured, via ileal fluid, revealing the amount of the compounds that would be colon-available upon leaving the small intestine
Summary
Endocannabinoids (ECs) and their structural congeners N-acylethanolamines (NAEs), known as “endocannabinoid-like molecules”, are endogenous lipid mediators involved in a wide range of biological pathways regulating appetite, nutrient metabolism, energy balance and inflammation [1, 2]. NAEs regulate food intake, glucose homeostasis and inflammation through activation of G protein-coupled receptors (GPCRs), peroxisome proliferator-activated receptors (PPAR-α), and transient receptor vanilloid potential receptors (TRVP) [9,10,11] Some of these receptors are located on cells lining in the gastro-intestinal tract (GIT). ECs, NAEs, and NAPEs are present in several foods [35], they increased in saliva upon food mastication in humans [36, 37] and the direct injections of NAPEs in the duodenum reduced food intake in mice [38] This evidence raised the question of whether the luminal content of ECs, NAEs, and NAPEs may be sufficient to elicit biological effects through the receptors located in the GIT. We determined the concentrations of ECs, NAEs and NAPEs in ileal fluids and plasma collected during an observational study in participants with ileostomy and investigated their relationship with habitual macronutrient and energy intake as well as with individual inflammatory status
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