Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding
Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding
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DOI：
10.1038/mp.2014.31
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发表时间：
2014-10-01
影响因子：
11
通讯作者：
Luquet, S.
中科院分区：
文献类型：
--
作者：
Cansell, C.;Castel, J.;Luquet, S.
循环甘油三酯（TGs）通常在饭后增加，但在病理生理条件下，如肥胖，会发生改变。尽管大脑中的TG代谢仍然知之甚少，但一些大脑结构表达处理富含TG颗粒的酶，包括中边缘结构。由于这个原因，并且因为高脂肪饮食的消耗改变了多巴胺信号，我们测试了TG可能直接针对中脑边缘奖励回路来控制寻求奖励行为的假设。我们发现，通过颈动脉向大脑输送少量TG会迅速减少自发运动和安非他明引起的运动，消除对美味食物的偏好，降低参与寻找食物行为的动机。相反，对伏隔核中tg水解酶脂蛋白脂肪酶的靶向破坏会增加对美味食物的偏好和觅食行为。最后，尽管持续的运动抑制，延长TG灌注导致恢复正常的美味食物偏好，这表明存在适应性机制。这些发现揭示了膳食脂肪可能改变中脑边缘回路功能和寻求奖励的新机制。
Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high-fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food-seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking.