ADIPOSE TISSUE DYSFUNCTION AND LIPOTOXICITY

肥胖与胰岛素抵抗、糖尿病和心血管问题有关。我们想知道肥胖为什么和如何导致这些问题，以及可以做些什么来预防或扭转它。为此，我们将研究这组病理之间的分子联系。我们认为，将肥胖与其他代谢疾病联系起来的机制之一与脂肪组织（脂肪）扩张和功能受损有关，导致其释放有毒的脂质，这些脂质会积聚并影响其他器官，如胰腺、肝脏和骨骼肌。具体来说，我们的目标是：a)了解使脂肪组织以“健康”方式生长的正常机制，而不会导致通常与肥胖相关的代谢问题，如糖尿病和心脏病发作；B)确定针对棕色脂肪组织（一种利用脂肪产生热量的脂肪）是否可以预防或逆转肥胖及其相关疾病；c)确定诊断性生物标志物，以确定发生并发症的风险以及致病的治疗靶向机制。为此，我们将使用小鼠模型和细胞，先进的实验研究和技术来验证我们最重要的发现，然后与我们的合作者一起在人类中证实它们。

Obesity is associated with insulin resistance, diabetes and cardiovascular problems. We want to know why and how obesity causes these problems and what can be done to either prevent or reverse it. For this purpose, we will investigate the molecular links between this cluster of pathologies. We think that one of the mechanisms that links obesity to other metabolic diseases is related to the impaired capacity of the adipose tissue (fat) to expand and function, causing it to release toxic lipid species that accumulate and affect other organs such as pancreas, liver and skeletal muscle.Specifically we aim to: a) understand the normal mechanisms enabling the adipose tissue to grow in a “healthy” way that does not result in the metabolic problems typically associated with obesity, such as diabetes and heart attacks; b) define whether targeting brown adipose tissue, a type of fat that uses fat to make heat, can prevent or reverse obesity and its associated diseases; and c) identify diagnostic biomarkers to identify the risk of developing complications as well as pathogenic therapeutically targetable mechanisms. For this purpose, we will use mouse models and cells, advanced experimental studies and technologies to validate our most significant findings before working with our collaborators to confirm them in humans.