title: Diet-dependent modulation of hippocampal expression of endocannabinoid signaling-related proteins in cannabinoid antagonist-treated obese rats.
abstract: 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 CB1 receptor by AM251 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 AM251 (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 AM251 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. AM251-treated rats fed the high-carbohydrate diet showed a reduction of the diacylglycerol lipase alpha : monoacylglycerol lipase ratio, whereas AM251-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 CB1 expression, AM251 induced specific changes focused in the CA1 stratum pyramidale of high-fat-diet-fed rats. These findings indicated that the cannabinoid antagonist AM251 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.
authors.affiliation: Laboratorio de Medicina Regenerativa, IBIMA-Hospital Carlos Haya (Pabellón de Gobierno), Málaga, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Luque-Rojas
authors.forename: Antoni
authors.initials: A
authors.lastname: Pastor
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavón
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: Ana
authors.initials: A
authors.lastname: Crespillo
authors.forename: Margarita
authors.initials: M
authors.lastname: Vida
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Grondona
authors.forename: Manuel
authors.initials: M
authors.lastname: Cifuentes
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bermúdez-Silva
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.forename: Fernando Rodríguez
authors.initials: FR
authors.lastname: de Fonseca
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D063388:Endocannabinoids; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D010739:Phospholipase D; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C103505:AM 251; C527163:Napepld protein, rat; C078814:anandamide