The role of adipose-derived extracellular vesicles in driving the impairment in skeletal muscle metabolic function and growth with ageing and obesity

随着年龄的增长，肌肉质量和功能的下降（肌肉减少症）以及伴随的肥胖增加是一个主要的医疗保健挑战，这会导致虚弱和慢性炎症性代谢紊乱，包括II型糖尿病（T2D）的发展。肌内和肌细胞内脂肪的积累加剧了胰岛素敏感性和肌肉质量的损害。重要的是，我们已经报道了人体肌肉暴露于肥胖的分泌组，（而非正常体重）脂肪组织损害肌肉生长，特别是在老年个体中，这表明肥胖脂肪组织和肌肉之间的病理性串扰在肌肉减少症的恶化中起核心作用。由于能够运输包括小的非编码RNA在内的货物，我们假设随着衰老，肥胖脂肪组织释放损害肌肉生长和肌肉代谢功能的病理性EV。这个奖学金的目的是双重的。首先，检测来自瘦和肥胖个体的这些脂肪EV的小RNA货物，其次确定脂肪EV对肌肉生长和功能的影响，以确定候选途径和药物靶点，用于开发治疗方法以对抗肌肉减少症。

The decline in muscle mass and function (sarcopenia) and accompanying increase in adiposity with ageing is a major healthcare challenge, that drives frailty and the development of chronic inflammatory metabolic disorders including Type II Diabetes (T2D). The accumulation of intramuscular and intramyocellular fat exacerbates both the impairment of insulin sensitivity and muscle mass. Importantly, we have reported that exposure of human muscle to the secretome from obese (but not normal-weight) adipose tissue impairs muscle growth, particularly in elderly individuals, suggesting that pathological cross-talk between obese adipose tissue and muscle plays a central role in the exacerbation of sarcopenia.With the recent discovery of extracellular vesicles (EVs) as mediators of cellular cross-talk, capable of transporting cargo including small non-coding RNAs, we hypothesise that with ageing, obese adipose tissue releases pathological EVs that impair muscle growth and muscle metabolic function. The aim of this studentship is two-fold. Firstly, to characterise the small RNA cargo of these adipose EVs from lean and obese individuals, and secondly to determine the effect of adipose EVs on muscle growth and function to identify candidate pathways and drug targets for the development of therapeutics to combat sarcopenia.