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 weight, brain endoplasmic reticulum (ER) stress signaling and brain inflammatory signaling, all critical contributors to obesity-associated hypertension pathogenesis. High fat diet-fed mice underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed ad libitum (S-AL) or were food restricted to match their body weight to VSG-operated mice (S-WM) in order to determine the role of body weight in the effect of VSG to lower blood pressure. Blood pressure was measured in freely-moving unstressed mice by radiotelemetry. VSG decreased energy intake, body weight and fat mass. Mean arterial blood pressure (MAP) was reduced in VSG compared with S-WM and S-AL. VSG-induced reductions in MAP were accompanied by a body weight-independent decrease in hypothalamic ER stress, hypothalamic inflammation and sympathetic tone. Gut microbial populations were assessed as a potential contributor, which revealed VSG-induced increases in the relative abundance of Gammaproteobacteria and Enterococcus, and decreases in Adlercreutzia. These results suggest that VSG reduces blood pressure, in part, independently of 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.
- Received August 15, 2016.
- Accepted January 4, 2017.
- © 2017. Published by The Company of Biologists Ltd
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