Laboratorio de Medicina Regenerativa, IBIMA-Hospital Carlos Haya (Pabellón de Gobierno), Málaga, Spain.
Eur J Neurosci. 2013 Jan;37(1):105-17. doi: 10.1111/ejn.12012. Epub 2012 Oct 4.
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.
饮食诱导的肥胖会引起内源性大麻素信号（ECS）的改变，影响能量平衡的调节。最近，我们证明，在高脂肪饮食喂养的大鼠中，AM251 阻断 CB1 受体不仅降低体重，还增加海马体中的成年神经发生，表明饮食对海马体大麻素功能的影响。为了进一步探讨海马 ECS 在高脂肪饮食诱导肥胖中的作用，我们研究了 AM251（3mg/kg）治疗的大鼠在三种不同饮食（标准饮食（正常饲料）、高碳水化合物饮食（70%碳水化合物）和高脂肪饮食（60%脂肪））下，产生（二酰基甘油脂肪酶α和 N-酰基磷脂乙醇胺磷脂酶 D）和降解（单酰基甘油脂肪酶和脂肪酸氨基水解酶）内源性大麻素的酶的免疫组织化学表达是否会改变。结果表明，AM251 减少了热量摄入和体重增加，并诱导了暴露于高热量饮食的动物海马体中 ECS 相关蛋白表达的调节。这些作用以饮食依赖的方式，分别限制在 2-花生四烯酰甘油或大麻素信号通路中。用高碳水化合物饮食喂养的 AM251 处理的大鼠表现出二酰基甘油脂肪酶α：单酰基甘油脂肪酶比值降低，而用高脂肪饮食喂养的 AM251 处理的大鼠表现出 N-酰基磷脂乙醇胺磷脂酶 D：脂肪酸氨基水解酶比值降低。这些结果与食物限制后发现的海马内源性大麻素水平降低一致。关于 CB1 表达，AM251 诱导了特定的变化，主要集中在高脂肪饮食喂养的大鼠海马 CA1 锥体层。这些发现表明，大麻素拮抗剂 AM251 以饮食特异性的方式调节大鼠海马体中的 ECS 相关蛋白。总的来说，这些结果表明，海马 ECS 参与了对不同热量饮食的生理适应。
