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

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