Subdiaphragmatic Vagotomy With Pyloroplasty Ameliorates the Obesity Caused by Genetic Deletion of the Melanocortin 4 Receptor in the Mouse
| Autor: | Joseph G. Verbalis, Kenneth L. Dretchen, Kimbell R Duncan, Richard A. Gillis, Jaclyn E. Tatge, Niaz Sahibzada, Ghazaul Dezfuli, Patrick G. Jackson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty food intake medicine.medical_treatment Pyloroplasty vagotomy lcsh:RC321-571 surgery 03 medical and health sciences body weight 0302 clinical medicine Weight loss Internal medicine energy expenditure medicine melanocortin Respiratory exchange ratio lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research business.industry General Neuroscience medicine.disease Vagotomy Obesity Melanocortin 4 receptor 030104 developmental biology Endocrinology Knockout mouse Melanocortin medicine.symptom weight loss business 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Frontiers in Neuroscience, Vol 12 (2018) Frontiers in Neuroscience |
| DOI: | 10.3389/fnins.2018.00104/full |
| Popis: | 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 vagal motor neurons. |
| Databáze: | OpenAIRE |
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