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Diet‐dependent modulation of hippocampal expression of endocannabinoid signaling‐related proteins in cannabinoid antagonist‐treated obese rats
Author(s) -
Rivera Patricia,
LuqueRojas María Jesús,
Pastor Antoni,
Blanco Eduardo,
Pavón Francisco J.,
Serrano Antonia,
Crespillo Ana,
Vida Margarita,
Grondona Jesús M.,
Cifuentes Manuel,
BermúdezSilva Francisco J.,
la Torre Rafael,
Fonseca Fernando Rodríguez,
Suárez Juan
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12012
Subject(s) - monoacylglycerol lipase , endocannabinoid system , diacylglycerol lipase , endocrinology , medicine , anandamide , cannabinoid receptor , hippocampal formation , lipoprotein lipase , biology , lipase , chemistry , biochemistry , receptor , antagonist , adipose tissue , enzyme
Diet‐induced obesity produces changes in endocannabinoid signaling ( ECS ), influencing the regulation of energy homeostasis. Recently, we demonstrated that, in high‐fat‐diet‐fed rats, blockade of CB 1 receptor by AM 251 not only reduced body weight but also increased adult neurogenesis in the hippocampus, suggesting an influence of diet on hippocampal cannabinoid function. To further explore the role of hippocampal ECS in high‐fat‐diet‐induced obesity, we investigated whether the immunohistochemical expression of the enzymes that produce (diacylglycerol lipase alpha and N ‐acyl phosphatidylethanolamine phospholipase D ) and degrade (monoacylglycerol lipase and fatty acid amino hydrolase) endocannabinoids may be altered in the hippocampus of AM 251 (3 mg/kg)‐treated rats fed three different diets: standard diet (normal chow), high‐carbohydrate diet (70% carbohydrate) and high‐fat diet (60% fat). Results indicated that AM 251 reduced caloric intake and body weight gain, and induced a modulation of the expression of ECS ‐related proteins in the hippocampus of animals exposed to hypercaloric diets. These effects were differentially restricted to either the 2‐arachinodoyl glycerol or anandamide signaling pathways, in a diet‐dependent manner. AM 251‐treated rats fed the high‐carbohydrate diet showed a reduction of the diacylglycerol lipase alpha : monoacylglycerol lipase ratio, whereas AM 251‐treated rats fed the high‐fat diet showed a decrease of the N ‐acyl phosphatidylethanolamine phospholipase D  : fatty acid amino hydrolase ratio. These results are consistent with the reduced levels of hippocampal endocannabinoids found after food restriction. Regarding the CB 1 expression, AM 251 induced specific changes focused in the CA 1 stratum pyramidale of high‐fat‐diet‐fed rats. These findings indicated that the cannabinoid antagonist AM 251 modulates ECS ‐related proteins in the rat hippocampus in a diet‐specific manner. Overall, these results suggest that the hippocampal ECS participates in the physiological adaptations to different caloric diets.

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