Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Eberhard Karls University of Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
Institute of Veterinary Physiology, University of Zurich, Winterthurerstraße 260, CH-8057 Zurich, Switzerland.
Int J Mol Sci. 2022 Jan 20;23(3):1126. doi: 10.3390/ijms23031126.
Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.
胃旁路手术（RYGB）已被证明在减肥和改善肥胖相关合并症方面取得了成功。高达 50%的患者会出现慢性并发症，如微量营养素吸收不良，这强调了需要额外的治疗方法。我们在液体蔗糖饮食诱导的肥胖大鼠模型中研究了全身性 RYGB 手术的效果。在摄入添加高液体蔗糖的饮食 8 周后，大鼠接受 RYGB 或对照假手术。RYGB、假手术配对喂养和假手术随意喂养组在恢复后继续进行饮食喂养。手术后，微生物群组成、炎症标志物、粪便、肝脏和血浆代谢物以及大脑神经元活性发生了显著改变。术后大鼠粪便中 4-氨基丁酸（GABA）升高，与拟杆菌门和的丰度升高相关，表明肠道神经系统（ENS）和肠道信号发生改变。RYGB 大鼠的 C 反应蛋白（CRP）、丝氨酸、甘氨酸和 3-羟基丁酸的血浆谱有利，提示肥胖风险得到逆转。液体蔗糖饮食和热量限制的影响主要表现在肝脏脂肪酸的变化上。我们的多模态方法揭示了 RYGB 手术后复杂的全身变化，并指出了肠道-大脑系统中的潜在治疗靶点，以模拟手术的作用模式。
