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Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-Induced Obesity

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Abstract

Background

We previously demonstrated vagal neural pathways, specifically subdiaphragmatic afferent fibers, regulate expression of the intestinal sodium-glucose cotransporter SGLT1, the intestinal transporter responsible for absorption of dietary glucose. We hypothesized targeting this pathway could be a novel therapy for obesity. We therefore tested the impact of disrupting vagal signaling by total vagotomy or selective vagal de-afferentation on weight gain and fat content in diet-induced obese rats.

Methods

Male Sprague–Dawley rats (n = 5–8) underwent truncal vagotomy, selective vagal de-afferentation with capsaicin, or sham procedure. Animals were maintained for 11 months on a high-caloric Western diet. Abdominal visceral fat content was assessed by magnetic resonance imaging together with weight of fat pads at harvest. Glucose homeostasis was assessed by fasting blood glucose and HbA1C. Jejunal SGLT1 gene expression was assessed by qPCR and immunoblotting and function by glucose uptake in everted jejunal sleeves.

Results

At 11-months, vagotomized rats weighed 19% less (P = 0.003) and de-afferented rats 7% less (P = 0.19) than shams. Vagotomized and de-afferented animals had 52% (P < 0.0001) and 18% reduction (P = 0.039) in visceral abdominal fat, respectively. There were no changes in blood glucose or glycemic indexes. SGLT1 mRNA, protein and function were unchanged across all cohorts at 11-months postoperatively.

Conclusions

Truncal vagotomy led to significant reductions in both diet-induced weight gain and visceral abdominal fat deposition. Vagal de-afferentation led to a more modest, but clinically and statistically significant, reduction in visceral abdominal fat. As increased visceral abdominal fat is associated with excess morbidity and mortality, vagal de-afferentation may be a useful adjunct in bariatric surgery.

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Acknowledgments

Funding sources include: Harvard Clinical Nutrition Center Grant P30-DK040561 (AT); Berkeley Fellowship and George Herbert Hunt Travelling Fellowship (ATS); and Nutricia Foundation Fellowship (AB). We would like to thank Dr Sharon Peled, and Dr Clare Tempany-Afdhal for technical advice and support with magnetic resonance image acquisition, and Jan Rounds for invaluable managerial support.

Conflict of interest

No authors have any conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    A. T. Stearns, A. Balakrishnan, S. W. Ashley & A. Tavakkolizadeh

  2. Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK

    A. T. Stearns

  3. Division of Gastroenterology, School of Clinical Sciences, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK

    A. Balakrishnan

  4. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    A. Radmanesh

  5. Pediatric Endocrine Unit, MassGeneral Hospital for Children, Harvard Medical School, Fruit Street, Boston, MA, 02114, USA

    D. B. Rhoads

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  1. A. T. Stearns
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Correspondence to A. Tavakkolizadeh.

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Stearns, A.T., Balakrishnan, A., Radmanesh, A. et al. Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-Induced Obesity. Dig Dis Sci 57, 1281–1290 (2012). https://doi.org/10.1007/s10620-011-1968-4

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  • DOI: https://doi.org/10.1007/s10620-011-1968-4

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