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

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
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 fat exacerbates both the impairment of insulin sensitivity and muscle mass. Importantly, we have reported that exposure of human muscle to the factors released from obese (but not normal-weight) fat tissue impairs muscle growth, particularly in elderly individuals, suggesting that cellular communication between fat tissue and muscle, via released factors from obese fat tissue, may play a central role in sarcopenia.
Recently, the discovery that nearly all cell types release small lipid particles (called extracellular vesicles or EVs) which can carry and transport cargo between different cells and tissues has provided a new understanding as to how cellular communication occurs between different tissues

We hypothesise that with ageing, obese fat tissue releases damaging EVs that impair muscle growth and muscle metabolic function. The aim of this studentship is two-fold. Firstly, to characterise the EVs released from fat tissue from lean and obese individuals by identifying their cargo, and secondly to determine the effect of these EVs on muscle growth and function. By doing so we will identify new biological pathways and potentially new targets to develop drugs to combat sarcopenia.