Endocannabinoid signal in the gut controls dietary fat intake
Endocannabinoid signal in the gut controls dietary fat intake
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DOI：
10.1073/pnas.1104675108
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发表时间：
2011-08-02
影响因子：
11.1
通讯作者：
Piomelli, Daniele
中科院分区：
文献类型：
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作者：
DiPatrizio, Nicholas V.;Astarita, Giuseppe;Piomelli, Daniele
口腔感觉信号驱动膳食脂肪摄入，但这一过程背后的神经机制在很大程度上是未知的。内源性大麻素系统因其在调节食物摄入、能量平衡和奖励方面的中枢和外周作用而受到关注。在这里，我们使用了一种假喂养模式，将口腔感觉与食物的进食后影响分离开来，以检验内源性大麻素信号是否参与脂肪摄入的正反馈控制。假性喂养脂基膳食通过改变控制内源性大麻素代谢的酶活性来刺激大鼠小肠近端内源性大麻素的动员。手术切除迷走神经可以消除这种影响，并且在其他外周器官或控制进食的大脑区域中没有观察到这种影响。假喂营养完全的液体食物产生了与脂肪相似的反应，而单独喂蛋白质或碳水化合物则没有这种效果。十二指肠局部输注cb1 -大麻素受体拮抗剂利莫那班可显著减少假喂养的脂肪。与利莫那班类似，全身给药外周限制性cb1受体拮抗剂URB 447可减轻脂质假性喂养。总的来说，这些结果表明，肠道内的内源性大麻素系统对脂肪摄入具有强大的调节控制作用，可能是抗肥胖药物的靶点。
Oral sensory signals drive dietary fat intake, but the neural mechanisms underlying this process are largely unknown. The endocannabinoid system has gained recent attention for its central and peripheral roles in regulating food intake, energy balance, and reward. Here, we used a sham-feeding paradigm, which isolates orosensory from postingestive influences of foods, to examine whether endocannabinoid signaling participates in the positive feedback control of fat intake. Sham feeding a lipid-based meal stimulated endocannabinoid mobilization in the rat proximal small intestine by altering enzymatic activities that control endocannabinoid metabolism. This effect was abolished by surgical transection of the vagus nerve and was not observed in other peripheral organs or in brain regions that control feeding. Sham feeding of a nutritionally complete liquid meal produced a similar response to that of fat, whereas protein or carbohydrate alone had no such effect. Local infusion of the CB1-cannabinoid receptor antagonist, rimonabant, into the duodenum markedly reduced fat sham feeding. Similarly to rimonabant, systemic administration of the peripherally restricted CB1-receptor antagonist, URB 447, attenuated sham feeding of lipid. Collectively, the results suggest that the endocannabinoid system in the gut exerts a powerful regulatory control over fat intake and might be a target for antiobesity drugs.