Brown adipose NADH oxidase for thermogenesis

肥胖已成为一种全球流行病，并与2型糖尿病和其他慢性疾病有关。当WAT是主要的能量储存器官时，棕色脂肪组织（BAT）通过非寒战产热来消耗能量以维持体温。最近，在实验室中发现了一种新的具有NADH氧化酶结构域的棕色脂肪特异性冷诱导蛋白。虽然这种NADH氧化酶与脂滴相关，但它在产热过程中定位于线粒体。本研究的假设是，通过NADH氧化，这种酶在棕色脂肪中发挥独特的作用，从NADH中再生NAD，以在细胞质中进行最佳的糖酵解，同时在产热过程中将电子转移到线粒体电子传递链。对最近产生的NADH氧化酶敲除小鼠的初步检查显示，随着肥胖的增加，产热功能受损。此外，在棕色脂肪细胞中产生过表达该NADH氧化酶蛋白的转基因小鼠，其产热能力增强。有了这些功能丧失和获得的小鼠模型，NADH氧化酶在冷诱导产热中的作用和潜在机制将被研究。

Obesity has become a global epidemic and is associated with type 2 diabetes and other chronic diseases. While WAT is the primary energy storage organ, brown adipose tissue (BAT) dissipates energy through non-shivering thermogenesis to maintain body temperature. Recently, a new brown fat specific cold inducible protein that has a NADH oxidase domain has been identified in the lab. While this NADH oxidase is lipid droplet associated, it localizes at the mitochondria during thermogenesis. The hypothesis of this research is that, through NADH oxidation, this enzyme uniquely functions in brown fat to regenerate NAD from NADH for optimal glycolysis in cytosol, while transferring electrons to mitochondrial electron transport chain, during thermogenesis. Initial examinations of NADH oxidase knockout mice that recently have generated show impaired thermogenesis with increased adiposity. In addition, transgenic mice overexpressing this NADH oxidase protein in brown adipocytes have been generated that showed enhanced thermogenesis. With these loss- and gain-of function mouse models in hand, the role and the underlying mechanism for this NADH oxidase in cold induced thermogenesis will be investigated.