title: Relative contributions of afferent vagal fibers to resistance to diet-induced obesity.
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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Stearns
authors.forename: A
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: A
authors.initials: A
authors.lastname: Radmanesh
authors.forename: S W
authors.initials: SW
authors.lastname: Ashley
authors.forename: D B
authors.initials: DB
authors.lastname: Rhoads
authors.forename: A
authors.initials: A
authors.lastname: Tavakkolizadeh
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000601:surgery; D000818:Animals; D001835:Body Weight; D002211:Capsaicin / Q000627:therapeutic use*; D003964:Diaphragm / Q000294:innervation / Q000503:physiopathology; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D007408:Intestinal Absorption; D050152:Intra-Abdominal Fat / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects*; D018689:Sensory System Agents / Q000627:therapeutic use; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D016896:Treatment Outcome; D014628:Vagotomy / Q000379:methods*; D014630:Vagus Nerve / Q000601:surgery
chemical_list: D018689:Sensory System Agents; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D005947:Glucose; D002211:Capsaicin