Circulating Endocannabinoids and N-acyl-ethanolamides in Patients with Sleep Apnea – Specific Role of Oleoylethanolamide

Abstract

Objective: The endocannabinoid system promotes diverse effects on fat and glucose metabolism as well as on energy balance and sleep regulation. The role of N-acylethanolamides like oleoylethanolamide (OEA) and other endocannabinoids such as anandamide (AEA) and 2-arachidonyl-glycerol (2-AG) has not yet been investigated in patients with sleep apnea.

Design and Methods: We measured circulating OEA, AEA and 2-AG in patients with sleep apnea (n=20) and healthy control subjects (n=57). Respiratory distress index (RDI) as measured by polysomnography was used as a quantitative index of sleep apnea.

Results: In patients with sleep apnea OEA serum concentrations were significantly higher than in control subjects (8.4 pmol/ml (95% CI 6.9;9.9) vs. 4.0 (3.5;4.5); p<0.0001, adjusted for body mass index (BMI), fasting insulin, HDL and LDL cholesterol). In contrast, AEA (2.9 (95% CI 1.9;3.9) vs. 1.8 (1.4;2.1), p=0.09) and 2-AG (20.0 (−14.5;54.5) vs. 32.8 (21.4;44.2), p=0.56) were not significantly different between patients with sleep apnea and control subjects after adjustment. In the sleep apnea group, OEA serum concentrations were associated with RDI (r²=0.28, p=0.02) and BMI (r²=0.32, p=0.01). However, OEA was not associated with BMI in the control group (p=0.10).

Conclusions: These results indicate that among the three analyzed fatty acid derivatives, OEA plays a specific role in patients with sleep apnea. Together with animal data, the 2-fold elevation of OEA serum concentrations could be interpreted as a neuroprotective mechanism against chronic oxidative stressors and a mechanism to promote wakefulness in patients with nocturnal sleep deprivation and daytime hypersomnolence.

Key words

endocannabinoids - oleoylethanolamide - anandamide - 2-arachidonyl-glycerol - sleep apnea

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1 These authors contributed equally

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