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Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

Citation

McGavigan, AK and Henseler, ZM and Garibay, D and Butler, SD and Jayasinghe, S and Ley, RE and Davisson, RL and Cummings, BP, Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice, Disease models & mechanisms, 10, (3) pp. 235-243. ISSN 1754-8403 (2017) [Refereed Article]


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Copyright Statement

2017. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1242/dmm.027474

Abstract

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 ad libitum 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 Enterococcus, and decreases in Adlercreutzia 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.

Item Details

Item Type:Refereed Article
Keywords:Vertical sleeve gastrectomy, Hypertension, ER stress, Mouse model
Research Division:Chemical Sciences
Research Group:Medicinal and Biomolecular Chemistry
Research Field:Medicinal and Biomolecular Chemistry not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
UTAS Author:Jayasinghe, S (Mr Sisitha Jayasinghe)
ID Code:135778
Year Published:2017
Web of Science® Times Cited:13
Deposited By:Health Sciences
Deposited On:2019-11-13
Last Modified:2019-12-13
Downloads:2 View Download Statistics

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