The Role of Fibro/Adipogenic Progenitors for Tongue Muscle Remodeling by High-Fat Diet Öffentlichkeit
Kim, Amy (Spring 2023)
Abstract
Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repeated episodes of upper airway collapse during sleep, resulting in fragmented sleep and oxygen deprivation. Although obesity is a major cause of OSA by increasing tongue fat, the cellular and molecular mechanisms underlying fat deposition in the tongue of OSA patients have not been well explored. We aim to establish a preclinical model of high-fat tongue in mice fed with a high-fat diet (HFD) for six months as a tool to study the impact of HFD-induced obesity on adipocytes and neuromuscular junctions (NMJs) in tongue muscles. The results demonstrated HFD-induced hypertrophy of adipocytes and denervation at NMJs in tongue muscles. Moreover, we revealed that a mesenchymal stem cell, named fibro/adipogenic progenitors, -derived bone morphogenetic protein-3b (BMP-3b) can drive these changes. BMP-3b maintains NMJ by stabilizing Schwann cells and inhibits the hypertrophy of adipocytes. Our data showed a lower level of Bmp3b expression in fibro/adipogenic progenitors of the tongue from HFD-fed mice compared to ND-fed mice. These findings provide important insight into the role of stem cells in the interplay between muscle remodeling, fat deposition, and denervation in the tongue in response to obesity and suggest potential therapeutic targets for OSA treatment. In addition, the study provides a valuable preclinical model for future research to understand the role of fibro/adipogenic progenitors in OSA and related conditions.
Table of Contents
INTRODUCTION 2
METHODS 4
RESULTS 8
DISCUSSION 12
REFERENCES 15
FIGURE LEGENDS 18
SUPPLEMENTAL FIGURE LEGENDS 21
FIGURES 22
SUPPLEMENTAL MATERIAL 27
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