FAAH deficiency promotes energy storage and enhances the motivation for food.
BACKGROUND
Fatty acid amide hydrolase (FAAH) is the main degrading enzyme of the fatty acid ethanolamides anandamide (AEA) and oleoylethanolamide (OEA), which have opposite effects on food intake and energy balance. AEA, an endogenous ligand of CB(1) cannabinoid receptors, enhances food intake and energy storage, whereas OEA binds to peroxisome proliferator-activated receptors-alpha to reduce food intake and promoting lipolysis. To elucidate the role of FAAH in food intake and energy balance, we have evaluated different metabolic and behavioral responses related to feeding in FAAH-deficient (FAAH(-/-)) mice and their wild-type littermates.


RESULTS
Total daily food intake was similar in both genotypes, but high-fat food consumption was enhanced during the dark hours and decreased during the light hours in FAAH(-/-) mice. The reinforcing and motivational effects of food were also enhanced in FAAH(-/-) mice as revealed by operant behavioral paradigms. These behavioral responses were reversed by the administration of the selective CB(1) cannabinoid antagonist rimonabant. Furthermore, body weight, total amount of adipose tissue, plasma-free fatty acids and triglyceride content in plasma, liver, skeletal muscle and adipose tissue, were increased in FAAH(-/-) mice. Accordingly, leptin levels were increased and adiponectin levels decreased in these mutants, FAAH(-/-) mice also showed enhanced plasma insulin and blood glucose levels revealing an insulin resistance. As expected, both AEA and OEA levels were increased in hypothalamus, small intestine and liver of FAAH(-/-) mice.


CONCLUSIONS
These results indicate that the lack of FAAH predominantly promotes energy storage by food intake-independent mechanisms, through the enhancement of AEA levels rather than promoting the anorexic effects of OEA.
Touriño
C
C
Laboratori de Neurofarmacologia, Departament de Ciències de Experimentals i de la Salut. Universitat Pompeu Fabra, PRBB, Barcelona, Spain.
Oveisi
F
F
Lockney
J
J
Piomelli
D
D
Maldonado
R
R
D050154:Adiposity / Q000502:physiology; D000581:Amidohydrolases / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors; D003216:Conditioning, Operant; D003624:Darkness; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects / Q000502:physiology; D063388:Endocannabinoids; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009042:Motivation; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D009829:Oleic Acids / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D000077285:Rimonabant; D014280:Triglycerides / Q000032:analysis; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D004041:Dietary Fats; D063388:Endocannabinoids; D009829:Oleic Acids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D000077285:Rimonabant; D014280:Triglycerides; D000099252:Fatty Acid Amide Hydrolases; C488250:oleoylethanolamide; C078814:anandamide