Endocannabinoid Anandamide Mediates the Effect of Skeletal Muscle Sphingomyelins on Human Energy Expenditure.

2018 Aug 2. doi: 10.1210/jc.2018-00780.
[Epub ahead of print]



Skeletal muscle endocannabinoids and sphingolipids (particularly, sphingomyelins) are inversely associated with sleeping energy expenditure (SLEEP) in humans. The endocannabinoid system may increase sphingolipid synthesis via cannabinoid receptor-1.


To investigate in human skeletal muscle whether endocannabinoids are responsible for the effect of sphingomyelins on SLEEP.


Muscle endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG), endocannabinoid congeners (oleoylethanolamide, OEA; palmitoylethanolamide, PEA) and sphingomyelin content were measured using liquid chromatography/mass spectrometry. SLEEP was assessed in a whole-room indirect calorimeter. Mediation analyses tested whether the inverse associations between sphingomyelins and SLEEP depended on endocannabinoids and endocannabinoid-related OEA and PEA.


Inpatient study.


Fifty-three overweight Native Americans.




AEA (r = 0.45, P = 0.001), 2-AG (r = 0.47, P = 0.0004), OEA (r = 0.27, P = 0.05) and PEA (r = 0.53, P < 0.0001) concentrations were associated with the total sphingomyelin content. AEA, OEA, and PEA correlated with specific sphingomyelins (SM18:1/23:0, SM18:1/23:1, and SM18:1/26:1) previously reported to be determinants of SLEEP in Native Americans (all r > 0.31, all P < 0.03). Up to 1/2 of the negative effect of these specific sphingomyelins on SLEEP was accounted by AEA (all P < 0.04), rendering the direct effect by sphingomyelin per se on SLEEP negligible (P > 0.05).


In skeletal muscle, AEA is responsible for the sphingomyelin effect on SLEEP, indicating that endocannabinoids and sphingomyelins may jointly reduce human whole-body energy metabolism.

PMID: 30113648
DOI: 10.1210/jc.2018-00780

LinkOut – more resources

Full Text Sources

  • Icon for Silverchair Information Systems

Tags: , , , , , ,