The John B. Pierce Laboratory, New Haven, CT 06519, USA.
Science. 2013 Aug 16;341(6147):800-2. doi: 10.1126/science.1239275.
Excessive intake of dietary fats leads to diminished brain dopaminergic function. It has been proposed that dopamine deficiency exacerbates obesity by provoking compensatory overfeeding as one way to restore reward sensitivity. However, the physiological mechanisms linking prolonged high-fat intake to dopamine deficiency remain elusive. We show that administering oleoylethanolamine, a gastrointestinal lipid messenger whose synthesis is suppressed after prolonged high-fat exposure, is sufficient to restore gut-stimulated dopamine release in high-fat-fed mice. Administering oleoylethanolamine to high-fat-fed mice also eliminated motivation deficits during flavorless intragastric feeding and increased oral intake of low-fat emulsions. Our findings suggest that high-fat-induced gastrointestinal dysfunctions play a key role in dopamine deficiency and that restoring gut-generated lipid signaling may increase the reward value of less palatable, yet healthier, foods.
膳食脂肪摄入过多会导致大脑多巴胺能功能下降。有人提出，多巴胺缺乏会通过引起代偿性过食来加剧肥胖，这是一种恢复奖赏敏感性的方式。然而，将长期高脂肪摄入与多巴胺缺乏联系起来的生理机制仍难以捉摸。我们发现，给予奥利诺胺，一种胃肠道脂质信使，其合成在长期高脂肪暴露后被抑制，足以恢复高脂肪喂养小鼠的肠道刺激多巴胺释放。向高脂肪喂养的小鼠给予奥利诺胺也消除了无味胃内喂养期间的动机缺陷，并增加了对低脂乳液的口服摄入。我们的研究结果表明，高脂肪引起的胃肠道功能障碍在多巴胺缺乏中起着关键作用，而恢复肠道产生的脂质信号可能会增加较不可口但更健康的食物的奖赏价值。
