Integrated Research and Treatment Centre for Adiposity Diseases, Department of Medicine, Universität Leipzig, Liebigstraße 21, 04103 Leipzig, Germany.
Department of General and Visceral, Vascular, and Paediatric Surgery, University of Würzburg, 97070 Würzburg, Germany.
Cell Metab. 2017 Feb 7;25(2):335-344. doi: 10.1016/j.cmet.2016.12.006. Epub 2017 Jan 5.
Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions. Mechanistically, interfering with local OEA, vagal, and dorsal striatal D1R signaling negated the beneficial effects of RYGB on fat intake and preferences. These findings delineate a molecular/systems pathway through which bariatric surgery improves feeding behavior and may aid in the development of novel weight loss strategies that similarly modify brain reward circuits compromised in obesity.
减重手术仍然是治疗病态肥胖的最有效长期治疗方法，主要通过尚未明确的机制降低热量摄入来实现。在这里，我们在大鼠中表明，类似于 Roux-en-Y 胃旁路术 (RYGB) 的摄入脂肪再路由会导致小肠下部产生脂肪饱腹感分子油酸乙醇酰胺 (OEA) 的减少。这与迷走神经驱动的背侧纹状体多巴胺释放增加有关。我们还证明，RYGB 在高脂肪饮食喂养条件下特异性地上调纹状体多巴胺 D1 受体 (D1R) 的表达。从机制上讲，干扰局部 OEA、迷走神经和背侧纹状体 D1R 信号会消除 RYGB 对脂肪摄入和偏好的有益影响。这些发现描绘了一条分子/系统途径，通过该途径，减重手术可以改善进食行为，并可能有助于开发新的减肥策略，这些策略同样可以改变肥胖症中受损的大脑奖励回路。
