PURPOSE:

Endocannabinoids (eCBs) and interleukin (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 eCBs-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 (39.3 ± 2.9 yrs; BMI = 21.1 ± 0.4), usually practicing aerobic exercise (8.1 ± 1.2 hours per week), and eight sedentary subjects (38.8 ± 3.7 yrs, BMI = 23.1 ± 0.8) 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 hours 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 per mg protein) significantly higher than those measured in the sedentary group (0.20 ± 0.02 pg/mL, and 42.0 ± 4.2 pmol/min per mg protein). Increased IL-6 levels paralleled increased FAAH activity, and consistently in vitro treatment of lymphocytes from sedentary individuals with 10 ng/mL IL-6 for 48 hours 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 CRE (cAMP response element)-like region in the human FAAH promoter. A mutation in the same element abolished IL-6 upregulation, demonstrating that this cytokine regulates FAAH activity at the transcriptional level.

CONCLUSIONS:

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

PMID:

 

23793235

 

[PubMed – as supplied by publisher]