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 CB1 cannabinoid receptors, enhances food intake and energy storage, whereas OEA binds to peroxisome proliferator-activated receptors-α 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.
Methodology and 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 CB1 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.
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.
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This study was supported by grants from European Communities (GENADDICT LSHM-CT-2004-005166 and PHECOMP LHSM-CT-2006-037669), National Institute on Drug Abuse (NIDA) (DA012413), Instituto de Salud Carlos III (RD06/001/001), Spanish Ministry of Education (SAF2007-64062) and Generalitat de Catalunya (2005SGR00131). CT was financed by FI and BE fellowships from AGAUR (Generalitat de Catalunya).
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Touriño, C., Oveisi, F., Lockney, J. et al. FAAH deficiency promotes energy storage and enhances the motivation for food. Int J Obes 34, 557–568 (2010). https://doi.org/10.1038/ijo.2009.262
- fatty acid amide hydrolase
- food intake
- body weight
- lipid turnover
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