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Med Sci Sports Exerc. 2014 Jan;46(1):24-32. doi: 10.1249/MSS.0b013e3182a10ce6.

The fatty acid amide hydrolase in lymphocytes from sedentary and active subjects.

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  • 11Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Rome, ITALY; 2Department of Movement, Human and Health Sciences, Foro Italico University of Rome, Rome, ITALY; 3Department of Biomedical Sciences, University of Teramo, Teramo, ITALY; 4Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, ITALY; and 5European Center for Brain Research/Santa Lucia Foundation, Rome, ITALY.



Endocannabinoids (eCB) and interleukin 6 (IL-6) levels change during physical activity, thus suggesting their involvement in the modulation of exercise-related processes like inflammation and energy homeostasis. To investigate whether lifestyle might affect the activity of the eCB-degrading enzyme fatty acid amide hydrolase (FAAH), active and sedentary subjects were enrolled.


Plasma IL-6 levels and lymphocyte FAAH activity of eight physically active male subjects (mean ± SEM; age = 39.3 ± 2.9 yr, body mass index = 21.1 ± 0.4 kg·m), usually practicing aerobic exercise (8.1 ± 1.2 h·wk), and eight sedentary subjects (38.8 ± 3.7 yr, body mass index = 23.1 ± 0.8 kg·m) were measured. Also, in vitro effect of IL-6 was tested on FAAH expression and activity and on FAAH promoter activity in lymphocytes from sedentary subjects.


Under resting conditions (at least 12 h from the last exercise), the active group showed plasma IL-6 levels (2.74 ± 0.73 pg·mL) and lymphocyte FAAH activity (215.7 ± 38.5 pmol·min·mg protein) significantly higher than those measured in the sedentary group (0.20 ± 0.02 pg·mL, and 42.0 ± 4.2 pmol·min·mg protein). Increased IL-6 levels paralleled increased FAAH activity, and consistently, the in vitro treatment of lymphocytes from sedentary individuals with 10 ng·mL IL-6 for 48 h significantly increased FAAH expression and activity. Transient transfection experiments showed that IL-6 induced the expression of a reporter gene under the control of a cAMP response element-like region in the human FAAH promoter. A mutation in the same element abolished IL-6 up-regulation, demonstrating that this cytokine regulates FAAH activity at the transcriptional level.


IL-6 leads to activation of the FAAH promoter, thus enhancing FAAH activity that modulates the eCB tone in physically active people.

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