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Relative contributions of afferent vagal fibers to resistance to diet-induced obesity.
Dig Dis Sci 2012; 57(5):1281-90DD

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+Show Affiliations

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22138962

Citation

Stearns, A T., et al. "Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-induced Obesity." Digestive Diseases and Sciences, vol. 57, no. 5, 2012, pp. 1281-90.
Stearns AT, Balakrishnan A, Radmanesh A, et al. Relative contributions of afferent vagal fibers to resistance to diet-induced obesity. Dig Dis Sci. 2012;57(5):1281-90.
Stearns, A. T., Balakrishnan, A., Radmanesh, A., Ashley, S. W., Rhoads, D. B., & Tavakkolizadeh, A. (2012). Relative contributions of afferent vagal fibers to resistance to diet-induced obesity. Digestive Diseases and Sciences, 57(5), pp. 1281-90. doi:10.1007/s10620-011-1968-4.
Stearns AT, et al. Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-induced Obesity. Dig Dis Sci. 2012;57(5):1281-90. PubMed PMID: 22138962.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relative contributions of afferent vagal fibers to resistance to diet-induced obesity. AU - Stearns,A T, AU - Balakrishnan,A, AU - Radmanesh,A, AU - Ashley,S W, AU - Rhoads,D B, AU - Tavakkolizadeh,A, Y1 - 2011/12/03/ PY - 2010/10/12/received PY - 2011/11/02/accepted PY - 2011/12/6/entrez PY - 2011/12/6/pubmed PY - 2012/7/12/medline SP - 1281 EP - 90 JF - Digestive diseases and sciences JO - Dig. Dis. Sci. VL - 57 IS - 5 N2 - 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. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/22138962/Relative_contributions_of_afferent_vagal_fibers_to_resistance_to_diet_induced_obesity_ L2 - https://doi.org/10.1007/s10620-011-1968-4 DB - PRIME DP - Unbound Medicine ER -