McGavigan Anne K, Henseler Zachariah M, Garibay Darline, Butler Scott D, Jayasinghe Sisitha, Ley Ruth E, Davisson Robin L, Cummings Bethany P
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Dis Model Mech. 2017 Mar 1;10(3):235-243. doi: 10.1242/dmm.027474. Epub 2017 Jan 12.
Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure-lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body mass, brain endoplasmic reticulum (ER) stress signaling and brain inflammatory signaling, which are all critical contributors to the pathogenesis of obesity-associated hypertension. Mice fed on a high-fat diet underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed or were food restricted to match their body mass to VSG-operated mice to determine the role of body mass in the ability of VSG to lower blood pressure. Blood pressure was then measured in freely moving unstressed mice by radiotelemetry. VSG decreased energy intake, body mass and fat mass. Mean arterial blood pressure (MAP) was reduced in VSG-operated mice compared with both sham-operated groups. VSG-induced reductions in MAP were accompanied by a body mass-independent decrease in hypothalamic ER stress, hypothalamic inflammation and sympathetic nervous system tone. Assessment of gut microbial populations revealed VSG-induced increases in the relative abundance of Gammaproteobacteria and , and decreases in These results suggest that VSG reduces blood pressure, but this is only partly due to the reduction in body weight. VSG-induced reductions in blood pressure may be driven by a decrease in hypothalamic ER stress and inflammatory signaling, and shifts in gut microbial populations.
减肥手术，如垂直袖状胃切除术（VSG），可显著改善心脏代谢健康，包括缓解高血压。然而，其背后的机制尚不清楚且研究较少。因此，我们开发并验证了首个VSG小鼠模型，该模型使用金标准无线电遥测技术再现了VSG的降压效果。我们使用这个模型来研究几种潜在机制，包括体重、脑内质网（ER）应激信号和脑炎症信号，这些都是肥胖相关高血压发病机制的关键因素。喂食高脂饮食的小鼠接受假手术或VSG手术并植入无线电遥测仪。对假手术小鼠进行喂食或限制食物摄入，使其体重与接受VSG手术的小鼠相匹配，以确定体重在VSG降低血压能力中的作用。然后通过无线电遥测技术在自由活动且无应激的小鼠中测量血压。VSG减少了能量摄入、体重和脂肪量。与两个假手术组相比，接受VSG手术的小鼠平均动脉血压（MAP）降低。VSG引起的MAP降低伴随着下丘脑ER应激、下丘脑炎症和交感神经系统张力的体重非依赖性降低。对肠道微生物群的评估显示，VSG导致γ-变形菌的相对丰度增加，而[此处原文缺失部分内容]减少。这些结果表明，VSG可降低血压，但这仅部分归因于体重的降低。VSG引起的血压降低可能是由下丘脑ER应激和炎症信号的减少以及肠道微生物群的变化驱动的。
