Understanding metabolic homeostasis and imbalance: What is the role of the endocannabinoid system?
Understanding metabolic homeostasis and imbalance: What is the role of the endocannabinoid system?
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DOI：
10.1016/j.amjmed.2007.06.007
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发表时间：
2007-09-01
影响因子：
5.9
通讯作者：
Kunos, George
中科院分区：
文献类型：
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作者：
Kunos, George
参与食欲调节的神经回路。 EC 产生食欲作用的位点之一涉及激活外侧下丘脑中的大麻素 1 (CB1) 受体，参与介导食物奖励的神经元从该受体投射到边缘系统。在肥胖动物模型中，CB1受体的药物阻断或基因消除会导致食物摄入量暂时减少，并伴有持续的体重减轻、肥胖减少和激素/代谢变化的逆转，例如血浆瘦素、胰岛素、葡萄糖和甘油三酯水平升高，以及血浆脂联素（Acrp30）水平降低。然而，CB1 阻断对体重和新陈代谢的有益作用不能仅用抑制食欲来解释。动物研究表明，CB1 阻断对脂肪代谢产生直接的外周和中枢影响。使用利莫那班阻断 CB1 受体不仅可以减轻体重和肥胖，还可以直接调节骨骼肌、脂肪组织和肝脏外周部位的脂肪代谢。临床前动物研究表明，CB1 阻断作用于脂肪细胞以增加 Acrp30 表达，作用于肝细胞以减少从头脂肪生成并增加脂肪酸氧化，作用于骨骼肌以降低血糖和胰岛素水平。从动物研究推断到临床，CB1 受体阻断提供了一种有前景的策略，不仅可以减轻体重和腹部肥胖，还可以预防和逆转其代谢后果。 (C) 2007 Elsevier Inc. 保留所有权利。
neural circuitry involved in appetite regulation. One of the sites of the orexigenic action of ECs involves activation of cannabinoid-1 (CB1) receptors in the lateral hypothalamus, from which neurons involved in mediating food reward project into the limbic system. In animal models of obesity, pharmacologic blockade or genetic ablation of CB1 receptors causes a transient reduction in food intake accompanied by sustained weight loss, reduced adiposity, and reversal of hormonal/metabolic changes, such as elevated levels of plasma leptin, insulin, glucose, and triglyceride, and reduced levels of plasma adiponectin (Acrp30). However, the beneficial effects of CB1 blockade on weight and metabolism cannot be explained by appetite suppression alone. Animal studies suggest that CB1 blockade exerts a direct peripheral as well as a central effect on fat metabolism. CB1 receptor blockade with rimonabant has been shown to not only reduce weight and adiposity but also to directly modulate fat metabolism at peripheral sites in skeletal muscle, adipose tissue, and the liver. Preclinical animal studies suggest that CB1 blockade acts on adipocytes to increase Acrp30 expression, on hepatocytes to decrease de novo lipogenesis and increase fatty acid oxidation, and on skeletal muscle to reduce blood glucose and insulin levels. Extrapolating from animal studies to the clinic, CB1 receptor blockade offers a promising strategy not only for reducing weight and abdominal adiposity but also for preventing and reversing its metabolic consequences. (C) 2007 Elsevier Inc. All rights reserved.