title: The fatty acid amide hydrolase in lymphocytes from sedentary and active subjects.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  IL-6 leads to activation of the FAAH promoter, thus enhancing FAAH activity that modulates the eCB tone in physically active people.
authors.affiliation: 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.
authors.forename: Valeria
authors.initials: V
authors.lastname: Gasperi
authors.forename: Roberta
authors.initials: R
authors.lastname: Ceci
authors.forename: Mirko
authors.initials: M
authors.lastname: Tantimonaco
authors.forename: Emanuela
authors.initials: E
authors.lastname: Talamonti
authors.forename: Natalia
authors.initials: N
authors.lastname: Battista
authors.forename: Attilio
authors.initials: A
authors.lastname: Parisi
authors.forename: Rita
authors.initials: R
authors.lastname: Florio
authors.forename: Stefania
authors.initials: S
authors.lastname: Sabatini
authors.forename: Antonello
authors.initials: A
authors.lastname: Rossi
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects* / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D057185:Sedentary Behavior; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D015850:Interleukin-6; D012333:RNA, Messenger; D000099252:Fatty Acid Amide Hydrolases