Brown adipose NADH oxidase for thermogenesis

棕色脂肪 NADH 氧化酶用于产热

基本信息

批准号：
10629810
负责人：
Hei Sook Sul
金额：
$ 38.66万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-09 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10629810
关键词：
Ablation Adipocytes Adipose tissue Adult Agonist Biochemical Biological Biological Assay Biology Biosensor Body Temperature Brown Fat Cell Fractionation Cells Chronic Disease Cytoplasm Cytosol Data Diabetes Mellitus Disease Management Electron Transport Electrons Energy Metabolism Enzymes Epidemic Exhibits Fasting Flavoproteins Glucose Glycolysis Hand Health Homeostasis Impairment Insulin Insulin Resistance Knockout Mice Lentivirus Lipids LoxP-flanked allele Measures Mediating Metabolic Metabolic syndrome Mitochondria Mus NADH NADH oxidase Natural regeneration Non-Insulin-Dependent Diabetes Mellitus Obesity Organ Oxygen Consumption Physiological Proteins Regulation Research Respiration Role Testing Thermogenesis Tissues Transgenic Mice adipocyte differentiation apoptosis inducing factor design diabetes control extracellular gain of function glucose metabolism improved in vivo insulin sensitivity interest mouse model mutant new therapeutic target novel overexpression oxidation small hairpin RNA subcutaneous

项目摘要

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.

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。尽管WAT是主要的能源储能器官，但棕色脂肪组织（BAT）通过不动的热生成来消散能量以维持体温。最近，在实验室中发现了一种具有NADH氧化酶结构域的新型棕色脂肪特异性诱导蛋白。尽管该NADH氧化酶是脂质液滴相关的，但在热发生过程中，它位于线粒体。这项研究的假设是，通过NADH氧化，该酶在棕色脂肪中独特起作用，从NADH再生NAD，以在热生成期间将电子转移到线粒体电子传输链中，以在细胞质中进行最佳糖酵解。最近对NADH氧化酶敲除小鼠进行的初步检查，这些小鼠最近产生了脂肪增强的热生成受损。另外，已经产生了棕色脂肪细胞中这种NADH氧化酶蛋白过表达的转基因小鼠，从而显示出增强的热生成。借助这些功能损失和获取的小鼠模型，将研究该NADH氧化酶在冷诱导的热发生中的作用和潜在机制。