title: Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice.
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 fedad libitumor 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 andEnterococcus, and decreases inAdlercreutziaThese 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.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Anne K
authors.initials: AK
authors.lastname: McGavigan
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.|Department of Microbiome Science, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
authors.forename: Zachariah M
authors.initials: ZM
authors.lastname: Henseler
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Darline
authors.initials: D
authors.lastname: Garibay
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Butler
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Sisitha
authors.initials: S
authors.lastname: Jayasinghe
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.|Department of Microbiome Science, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.|Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Davisson
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA bpc68@cornell.edu.
authors.forename: Bethany P
authors.identifier: 0000-0002-0610-9870
authors.initials: BP
authors.lastname: Cummings
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002432:Cecum / Q000382:microbiology; D059865:Endoplasmic Reticulum Stress; D002149:Energy Intake; D005215:Fasting / Q000097:blood; D005743:Gastrectomy; D000069196:Gastrointestinal Microbiome; D054439:Ghrelin / Q000097:blood; D007031:Hypothalamus / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D020738:Leptin / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000097:blood; D015398:Signal Transduction
chemical_list: D054439:Ghrelin; D020738:Leptin; D009638:Norepinephrine
keywords: ER stress; Hypertension; Mouse model; Vertical sleeve gastrectomy