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−2), usually practicing aerobic exercise (8.1 ± 1.2 h·wk−1), and eight sedentary subjects (38.8 ± 3.7 yr, body mass index = 23.1 ± 0.8 kg·m−2) 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−1) and lymphocyte FAAH activity (215.7 ± 38.5 pmol·min−1·mg−1 protein) significantly higher than those measured in the sedentary group (0.20 ± 0.02 pg·mL−1, and 42.0 ± 4.2 pmol·min−1·mg−1 protein). Increased IL-6 levels paralleled increased FAAH activity, and consistently, the in vitro treatment of lymphocytes from sedentary individuals with 10 ng·mL−1 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.
1Department 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
Address for correspondence: Valeria Gasperi, PhD, Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy; E-mail: firstname.lastname@example.org. Mauro Maccarrone, MS, PhD, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome (Italy); E-mail: email@example.com.
Submitted for publication January 2013.
Accepted for publication June 2013.