The Fatty Acid Amide Hydrolase in Lymphocytes from Sedentary and Active Subjects.

• Autores: Antonello Rossi, Mauro Maccarrone, Valeria Gasperi, Roberta Ceci, Mirko Tantimonaco, Emanuela Talamonti, Natalia Battista, Attilio Parisi, Rita Florio, Stefania Sabatini
• Localización: Medicine & Science in Sports & exercise: Official Journal of the American College of Sports Medicine, ISSN 0195-9131, Vol. 46, Nº. 1, 2014, págs. 24-32
• Idioma: inglés
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• Resumen

  • AB 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[middle dot]m-2), usually practicing aerobic exercise (8.1 +/- 1.2 h[middle dot]wk-1), and eight sedentary subjects (38.8 +/- 3.7 yr, body mass index = 23.1 +/- 0.8 kg[middle dot]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[middle dot]mL-1) and lymphocyte FAAH activity (215.7 +/- 38.5 pmol[middle dot]min-1[middle dot]mg-1 protein) significantly higher than those measured in the sedentary group (0.20 +/- 0.02 pg[middle dot]mL-1, and 42.0 +/- 4.2 pmol[middle dot]min-1[middle dot]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[middle dot]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