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Front. Neurosci. | doi: 10.3389/fnins.2018.00104

Subdiaphragmatic Vagotomy with Pyloroplasty Ameliorates the Obesity Caused by Genetic Deletion of the Melanocortin 4 Receptor in the Mouse

 Ghazaul Dezfuli1, Richard A. Gillis1, Jaclyn E. Tatge1, Kimbell Rush Duncan2, Kenneth Dretchen1, Patrick Jackson3,  Joseph G. Verbalis4 and  Niaz Sahibzada1*
  • 1Pharmacology & Physiology, Georgetown University, United States
  • 2Georgetown University, United States
  • 3Department of Surgery, Georgetown University, United States
  • 4Department of Medicine, Georgetown University, United States

ABSTRACT
Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice (Mc4r -/-).
Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r -/-mice. Results: In the first study, SDV prevented > 20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study. Initially, SDV mice had reduced weekly FI; however, FI normalized to that of controls and baseline FI within the 8-week study period. In the second study, the severe obesity that is characteristic of the adult Mc4r -/- genotype was significantly improved by SDV with a magnitude of 30% loss in excess BW over a 4-week period. Consistent with the first preventative study, within the treatment arm, SDV mice also demonstrated a transient reduction in FI relative to control and baseline levels that normalized over subsequent weeks. In addition to the accompanying loss in weight, mice subjected to SDV showed a decrease in respiratory exchange ratio (RER), and an increase in locomotor activity (LA). Analysis of the white fat-pad deposits of these mice showed that they were significantly less than the control groups. Conclusions: Altogether, our data demonstrates that SDV both prevents gain in BW and causes weight loss in severely obese Mc4r -/- mice. Moreover, it suggests that an important aspect of weight reduction for this type of monogenic obesity involves loss of signaling in the efferent vagal motor neurons.

Keywords: Vagotomy, Weight Loss, Surgery, melanocortin, food intake, Body Weight, Energy Expenditure

Received: 15 Sep 2017; Accepted: 12 Feb 2018.

Edited by:

Elisabeth Lambert, Swinburne University of Technology, Australia

Reviewed by:

Laurent Gautron, University of Texas Southwestern Medical Center, United States
Denis Richard, Laval University, Canada
Brian Y. Lam, University of Cambridge, United Kingdom  

Copyright: © 2018 Dezfuli, Gillis, Tatge, Rush Duncan, Dretchen, Jackson, Verbalis and Sahibzada. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Niaz Sahibzada, Georgetown University, Pharmacology & Physiology, 3900 Reservoir Road NW, Washington, 20057, DC, United States, sahibzan@georgetown.edu