Cell：高蛋白膳食如何使大脑形成饱腹感？

一顿高蛋白大餐后，我们通常有一种饱腹感，最具代表性的就是皮带越来越紧的不舒服感，其实饱腹感涉及的内容不仅仅是这样，那么，这种饱腹感是如何产生的了？发表于7月5日Cell上的一篇研究解答了上述问题，它把消化道与大脑之间的饱足感信号通路描绘了出来，了解大脑与消化道间的这种往返回路可能为将来肥胖症治疗和预防铺平道路。

食物摄入由神经纤维上的Mu阿片受体（MORs，也可结合吗啡）调节，该受体主要分布于门静脉壁上，其中门静脉是回收消化道血液的主要血管。具体地说，刺激受体增加食物摄入，阻断受体则抑制摄入。经研究，研究人员发现肽（即膳食蛋白消化后产物）能阻断MORs，从而抑制食欲。肽发送信号传至大脑，信号再传回消化道，刺激小肠释放葡萄糖，抑制进食欲望。

用基因工程方法使小鼠MORs缺陷，这种小鼠在吃高蛋白食物后，就不能进行葡萄糖释放，也没有表现出饱足的迹象。若给予MOR激动剂或抑制剂，也不影响它们的食物摄入，这与正常小鼠不同。因为MORs也存在于人门静脉内壁的神经元细胞中，所以这种新发现的机制也可能发生在人。一直以来，大家都知道蛋白质膳食的饱腹效果，却无法解释这种现象，该研究结果正好给此现象作出了解释，也为食物摄入与饥饿感控制提供了一种新见解，还可能为将来治疗肥胖症提供一种新方法。

doi:10.1016/j.cell.2012.05.039
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Mu-Opioid Receptors and Dietary Protein Stimulate a Gut-Brain Neural Circuitry Limiting Food Intake

Celine Duraffourd,Filipe De Vadder,Daisy Goncalves,Fabien Delaere,Armelle Penhoat,Bleuenn Brusset,Fabienne Rajas,Dominique Chassard,Adeline Duchampt,Anne Stefanutti,Amandine Gautier-Stein,Gilles Mithieux

Intestinal gluconeogenesis is involved in the control of food intake. We show that mu-opioid receptors (MORs) present in nerves in the portal vein walls respond to peptides to regulate a gut-brain neural circuit that controls intestinal gluconeogenesis and satiety. In vitro, peptides and protein digests behave as MOR antagonists in competition experiments. In vivo, they stimulate MOR-dependent induction of intestinal gluconeogenesis via activation of brain areas receiving inputs from gastrointestinal ascending nerves. MOR-knockout mice do not carry out intestinal gluconeogenesis in response to peptides and are insensitive to the satiety effect induced by protein-enriched diets. Portal infusions of MOR modulators have no effect on food intake in mice deficient for intestinal gluconeogenesis. Thus, the regulation of portal MORs by peptides triggering signals to and from the brain to induce intestinal gluconeogenesis are links in the satiety phenomenon associated with alimentary protein assimilation.