Modelling hyperplastic and hypertrophic adipose tissue growth in zebrafish

脂肪组织(AT)通过两种机制生长。增生性生长是脂肪细胞数量的增加，而肥厚性生长是细胞大小的增加。衰老和过度和不平衡的能量消耗会导致脂肪细胞增殖减少，肥大加剧。这种脂肪组织扩张的方法在代谢上是不健康的，经常会导致胰岛素抵抗、免疫细胞募集、抗炎细胞因子减少、促炎细胞因子增加和血脂异常。CEBPA是脂肪形成的关键调节因子。我们课题组的早期数据表明，斑马鱼CEBPA基因功能缺失或功能降低会导致AT生长功能障碍，从而导致组织出现过早衰老的迹象，如祖细胞数量减少，AT总面积减少和增殖减少。因此，我们假设CEBPA功能降低会导致前体细胞衰老增加、脂肪重塑失败、脂肪细胞坏死和整个脂肪的炎性损伤反应。该博士学位的目的是利用斑马鱼模型和多种成像技术来研究与衰老有关的肥大和肥大脂肪重构动力学，并利用这些数据来建立脂肪组织扩张的数学模型。

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.