Skeletal muscle and adipose cross talk identifying novel mediators of insulin sensitivity

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The role of candidate adipose/muscle cross-talk mediators in mediating cellular metabolism and insulin signalling activity in human tissues is not well established. In order to identify the key cross-talk mediators and to validate their role in regulating cellular metabolism and insulin signalling pathways it is critical to initially conduct such studies using human derived primary cells, and then to back-translate these findings into appropriate in vivo models. The objective of this studentship is to investigate the role of muscle/adipose cellular cross talk and its effect of skeletal muscle metabolic phenotype and insulin signalling so that new targets which mediate insulin sensitivity and cellular metabolism can be identified and validated in preclinical models. Mechanistic adipose and muscle cellular cross-talk studies have predominantly been performed using murine cells (e.g C2C12 cell line), which are not suitable for target identification studies due to their different metabolic phenotype. Importantly, for this study we have a substantial and growing collection of human muscle and patient-matched adipose samples from both lean and obese individuals. Furthermore, in vitro cellular cross-talk studies will be conducted using primary human myotubes and patient-matched adipocytes. We will then back-translate these findings into appropriate animal models in order to perform in vivo target validation studies. The objectives of this project are therefore as follows. 1. To identify novel adipose/muscle cross-talk mediators through lipidomic and proteomic mass-spectroscopy analysis of human adipose tissue from both normal weight and obese individuals 2. Establish bespoke ex vivo models of human adipose/muscle cross-talk 3. Validate using appropriate models novel mediators of adipose/muscle cross-talk in regulating cellular metabolic phenotype and insulin sensitivity