Circulating endocannabinoids and N-acyl-ethanolamides in patients with sleep apnea--specific role of oleoylethanolamide.
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.


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 (r (2) = 0.28, p = 0.02) and BMI (r (2) = 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.
Jumpertz
R
R
Department of Internal Medicine, University of Leipzig, Germany.
Wiesner
T
T
Blüher
M
M
Engeli
S
S
Bátkai
S
S
Wirtz
H
H
Bosse-Henck
A
A
Stumvoll
M
M
D001095:Arachidonic Acids / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D063385:Cannabinoid Receptor Modulators / Q000032:analysis / Q000097:blood*; D016022:Case-Control Studies; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009829:Oleic Acids / Q000097:blood* / Q000502:physiology*; D053284:Polyunsaturated Alkamides / Q000097:blood; D012891:Sleep Apnea Syndromes / Q000097:blood*
D001095:Arachidonic Acids; D001786:Blood Glucose; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D007328:Insulin; D008055:Lipids; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; C094503:glyceryl 2-arachidonate; C078814:anandamide