Modelling hyperplastic and hypertrophic adipose tissue growth in zebrafish

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Adipose tissue (AT) grows through two mechanisms. Hyperplastic growth which is an increase in the number of adipocytes while hypertrophic growth is an increase in cell size. Aging and excessive and unbalanced energy consumption trigger a reduction in hyperplasia amongst adipocytes and elevated hypertrophy. This method of adipose tissue expansion is metabolically unhealthy, often leading to insulin resistance, immune cell recruitment, reduction in anti-inflammatory cytokines, increase in pro-inflammatory cytokines and dyslipidaemia. CEBPA, is a key mediator of adipogenesis. Early data from our group suggests that a loss or reduced function of the cebpa gene in Zebrafish leads to dysfunction within AT growth, whereby the tissue presents signs of premature aging such as lower progenitor number, reduced overall AT area and reduced hyperplasia. Thus, we hypothesise lowered cebpa function leads to increased progenitor senescence, a failure in adipose remodelling, adipocyte necrosis and an adipose-wide inflammatory injury response. The aim of this PhD is to utilise the Zebrafish model and numerous imaging techniques in order to investigate hyperplastic and hypertrophic adipose remodelling dynamics become defective in relation to ageing as well as utilise this data to produce a mathematical model for adipose tissue expansion.