Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?

Silvia Tagliamonte, Chris I R Gill, L Kirsty Pourshahidi, Mary M Slevin, Ruth K Price, Rosalia Ferracane, Roger Lawther, Gloria O'Connor, Paola Vitaglione, Silvia Tagliamonte, Chris I R Gill, L Kirsty Pourshahidi, Mary M Slevin, Ruth K Price, Rosalia Ferracane, Roger Lawther, Gloria O'Connor, Paola Vitaglione

Abstract

Purpose: To 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.

Methods: An 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.

Results: Regarding 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.

Conclusion: We 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 website: NCT04143139; www.clinicaltrials.gov .

Keywords: Gastrointestinal receptors; Ileal fluids; Ileostomists; Lipid mediators; N-acylethanolamines; Nutrient sensing.

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Participants flow
Fig. 2
Fig. 2
N-acylethanolamines (a) and N-acylphosphatidylethanolamines (b) concentrations in ileal fluids from the overall population (n = 35), LEA (c) and OEA (d) concentrations in ileal fluids from men (M, empty dots; n = 17) and women (W, solid dots; n = 18) and PEA (e) concentrations in ileal fluids from participants with normalweight (NW; n = 11), overweight (OW; n = 12) and obesity. Different letters on the box plots indicate p value < 0.05 by One-way ANOVA and Bonferroni adjustement for multiple comparisons or by Student’s t test. Total NAEs include the sum of LEA, OEA, PEA and SEA. LEA Linoylethanolamide, OEA oleoylethanolamide, PEA palmitoylethanolamide, SEA stearoylethanolamide, NAEs N-acylethanolammines, NAPEs N-acylphosphatidylethanolamines. The box plots show the data distribution based on first quartile, median and third quartile
Fig. 3
Fig. 3
Plasma Endocannabinoids (a), N-acylethanolammines (b) and N-acylphosphatidylethanolamines (c) concentrations in the overall population (n = 35) and N-acylphosphatidylethanolamines (d) plasma concentrations from participants with normalweight (NW; n = 11), overweight (OW; n = 12) and obesity (OB, n = 11). Different letters on the box plots indicate p value < 0.05 by One-way ANOVA and Bonferroni adjustement for multiple comparisons. Total ECs include the sum of 2-AG and AEA; total NAEs include the sum of LEA, OEA, PEA and SEA. 2-AG 2-Arachidonoylglicerol, AEA arachidonoylethanolamide, ECs endocannabinoids, LEA linoylethanolamide, OEA oleoylethanolamide, PEA palmitoylethanolamide, SEA stearoylethanolamide, NAEs N-acylethanolammines, NAPEs N-acylphosphatidylethanolamines. The box plots show the data distribution based on first quartile, median and third quartile
Fig. 4
Fig. 4
Correlation between individual plasma concentrations of PEA (a), BMI (b) and individual serum CRP. Men (M, n = 17) are indicated with empty dots and women (W, n = 18) with solid dots. R and p value are assessed by Pearson correlation on ln transformed variables. PEA palmitoylethanolamide, CRP C-reactive protein, BMI Body Mass Index

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