Vagal innervation patterns following Roux-en-Y gastric bypass in the mouse

Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, TX, USA.
International journal of obesity (2005) (Impact Factor: 5.22). 03/2013; 37(12). DOI: 10.1038/ijo.2013.48
Source: PubMed

ABSTRACT This study investigated the anatomical integrity of the vagal innervation to the gastrointestinal tract following Roux-en-Y gastric bypass (RYGB) in the mouse. Specifically, the surgical procedure was performed in high-fat-fed reporter mice (Phox2b-Cre-tdTomato), in which the entire vagal innervation of the gastrointestinal tract was fluorescently labeled. As a result, our anatomical observations revealed both qualitative and quantitative changes of the vagal supply to the gut after RYGB. This included the extensive denervation of the glandular and distal stomach, and sites of surgical interventions (clipping and anastomosis). Furthermore, the stomach wall after RYGB frequently contained dystrophic axons and endings, suggestive of vagal neurodegeneration. In contrast, RYGB did not significantly modify the innervation to the rest of the intestines and glucostatic organs. In summary, the present study describes a previously unrecognized pattern of vagal remodeling and denervation following RYGB. Our findings may serve as a guideline for future investigations on the role of gut-brain communication in bariatric surgery.International Journal of Obesity advance online publication, 23 April 2013; doi:10.1038/ijo.2013.48.

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    ABSTRACT: Bariatric surgical procedures such as vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most potent treatments available to produce sustained reductions in body weight and improvements in glucose regulation. While traditionally these effects are attributed to mechanical aspects of these procedures, such as restriction and malabsorption, a growing body of evidence from mouse models of these procedures points to physiological changes that mediate the potent effects of these surgeries. In particular, there are similar changes in gut hormone secretion, bile acid levels, and composition after both of these procedures. Moreover, loss of function of the nuclear bile acid receptor (FXR) greatly diminishes the effects of VSG. Both VSG and RYGB are linked to profound changes in the gut microbiome that also mediate at least some of these surgical effects. We hypothesize that surgical rearrangement of the gastrointestinal tract results in enteroplasticity caused by the high rate of nutrient presentation and altered pH in the small intestine that contribute to these physiological effects. Identifying the molecular underpinnings of these procedures provides new opportunities to understand the relationship of the gastrointestinal tract to obesity and diabetes as well as new therapeutic strategies to harness the effectiveness of surgery with less-invasive approaches. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell Metabolism 02/2015; DOI:10.1016/j.cmet.2015.01.001 · 16.75 Impact Factor
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    ABSTRACT: This study investigated the anatomical integrity of vagal innervation of the gastrointestinal tract following vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations. The retrograde tracer fast blue (FB) was injected into the stomach to label vagal neurons originating from nodose ganglion (NG) and dorsal motor nucleus of the vagus (DMV). Microglia activation was determined by quantifying changes in the fluorescent staining of hindbrain sections against an ionizing calcium adapter binding molecule 1 (Iba1). Reorganization of vagal afferents in the hindbrain was studied by fluorescent staining against isolectin 4 (IB4). The density of Iba1- and IB4-immunoreactivity was analyzed using Nikon Elements software. There was no difference in the number of FB-labeled neurons located in NG and DMV between VSG and VSG-sham rats. RYGB, but not RYGB-sham rats, showed a dramatic reduction in number of FB-labeled neurons located in the NG and DMV. VSG increased, while the RYGB operation decreased, the density of vagal afferents in the nucleus tractus solitarius (NTS). The RYGB operation, but not the VSG procedure, significantly activated microglia in the NTS and DMV. Results of this study show that the RYGB, but not the VSG procedure, triggers microglia activation in vagal structures and remodels gut-brain communication.
    01/2015; 2015:1-9. DOI:10.1155/2015/601985
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    ABSTRACT: Background-We investigated the hypothesis that the favorable effects of gastrointestinal (GI) intervention on hypertension (HTN) and cardiovascular (CV) disturbances are mediated by antagonizing overdrive of the sympathetic nervous system (SNS). Methods and Results-Hypertensive patients with metabolic disturbances underwent laparoscopic Roux-en-Y gastric bypass surgery, and spontaneously hypertensive rats (SHRs) underwent RYGB or sham surgery. Blood pressure (BP), heart rate (HR), endothelium-dependent flow-mediated dilation, and anthropometric as well as laboratory parameters were measured at baseline and during follow-up. Changes of BP and HR in response to cold stress, renal sympathetic nervous activity (RSNA), vasoconstriction induced by electrical field stimulation, microinjection of nucleus of the solitary tract (NTS), and CV function and structure were examined in SHRs with or without surgery. Compared with baseline, BP and HR were significantly reduced in both hypertensive patients with type 2 diabetes and rats. Impaired endothelial-dependent vasodilatation and metabolic disturbances in hypertensive patients were also ameliorated after surgery. CV disturbances were reversed by surgery in SHRs. Under acute cold exposure, the variations in BP and HR were smaller in surgically treated SHRs, compared to sham SHRs. RSNA and vasoconstriction induced by perivascular nerve stimulation as well as NTS-mediated changes of BP were decreased in surgically treated SHRs, compared to sham SHR. Weight loss did not affect BP and RSNA in sham SHRs. Conclusions-GI intervention ameliorates HTN in both hypertensive patients and rats by inhibiting overdrive of the SNS. Therefore, targeting gastrointestine could be a novel strategy to treat HTN with metabolic disturbances.
    Journal of the American Heart Association 09/2014; 3(5). DOI:10.1161/JAHA.114.000929


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