Modulation of Intramuscular Fat Remodeling by GDF10 in High-Fat Diet-Induced Obesity Público

Abstract

Obesity is becoming an epidemic health concern, significantly impacting skeletal muscle health through increased fatty infiltration and weakened muscle strength. Our study investigates the effects of high fat diet (HFD)-induced obesity on muscle health, evaluating the fatty infiltration, neuromuscular connection, and muscle strength. One of the main contributors of intramuscular adipogenesis is fibro-adipogenic progenitors (FAPs), which differentiate into adipocytes or fibroblasts depending on different cytokine signaling. However, FAPs also express high level of growth differentiation factor 10 (GDF10) that is known to promote neuromuscular junction integrity and negatively correlated with the level of fat accumulation. Therefore, we target GDF10 to examine its potential therapeutic effect in mitigating obesity-induced muscle damages. Utilizing both tibialis anterior (TA) and tongue muscles from the mice models, we assessed the impact of GDF10 overexpression in reducing fat infiltration and preserving limb muscle function. Our results indicate that HFD significantly exacerbates fatty infiltration and NMJ denervation in muscle tissues, leading to the decline in muscle grip strength. GDF10 overexpression was found to reduce adipocyte size in both glycerol-injured TA and HFD-fed Tongue muscles, suggesting its role in inhibiting adipocyte hypertrophy in muscles. Our findings contribute to understanding the mechanisms of obesity-induced muscle remodeling and support further research into GDF10 as a potential intervention for maintaining muscle health in obese individuals.

Table of Contents

Introduction 1

Materials and Methods 3

Result 7

Discussion 11

Reference 14

Figure Legends 16

Figures 19

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Cell
Palavra-chave	Growth Differentation Factor 10 Glycerol injury Fibro/Adipogenic Progenitors Satellite cells
Committee Chair / Thesis Advisor	Choo, Hyojung, Emory University
Committee Members	Jang, Young, Emory University Comstra, Skye, Emory University

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