权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of Mitochondrial Biogenesis and Function by DsbA-L in the Liver

DsbA-L 在肝脏中对线粒体生物发生和功能的调节

基本信息

批准号：
10251019
负责人：
ALAN FRAZER
金额：
$ 33.98万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251019
关键词：
Affect Animal Model Binding Binding Sites Biogenesis Biology Cardiovascular Diseases Cells Chronic Cyclic GMP DNA DNA Packaging DNA biosynthesis Deacetylation Development Down-Regulation Energy Metabolism Epidemic Escherichia coli Fatty Liver Glutathione S-Transferase Grant Hepatic Hepatocyte High Fat Diet Homeostasis Impairment In Vitro Inflammation Inflammatory Insulin Insulin Resistance Knock-out Knowledge Lead Light Link Lipids Liver Liver Dysfunction Liver Mitochondria Liver diseases Mediating Metabolic Metabolic Diseases Metabolic dysfunction Mitochondria Mitochondrial DNA Mitochondrial Matrix Molecular Molecular Chaperones Mus Names Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Oxidation-Reduction Oxidoreductase Pathway interactions Physiological Play Protein Acetylation Protein Deficiency Proteins Rattus Regulation Research Resistance Role Sterility Stress Structure Testing adenoviral-mediated diet-induced obesity disulfide bond enzyme activity factor A gain of function human subject in vivo knockout animal liver function mitochondrial dysfunction mtTF1 transcription factor mutant novel therapeutic intervention novel therapeutics obesity prevention overexpression protein expression therapy resistant transcription factor

项目摘要

Abstract Mitochondria in hepatocytes play a major role in maintaining whole-body energy metabolism and normal function of the liver. Impaired mitochondrial function is closely associated with various metabolic diseases such as obesity, insulin resistance, and hepatosteatosis. However, the precise underlying mechanisms remain to be fully elucidated. Filling this major gap of knowledge will yield new information on the mechanisms underlying mitochondrial dysfunction-associated liver diseases, insulin resistance, and type 2 diabetes. Our current study focuses on the functional roles and mechanisms of action of the disulfide-bond-A oxidoreductase-like protein (DsbA-L). We recently found that DsbA-L expression is significantly reduced in the liver of obese human subjects and diet-induced obese mice. In addition, loss- and gain-of-function studies reveal that DsbA-L is a key regulator of mitochondrial integrity and function and its deficiency in the liver plays an important role in obesity-induced hepatosteatosis and metabolic dysfunction. In the current study, we will use molecular and cellular approaches as well as knockout animal models to elucidate the mechanisms regulating mitochondrial integrity and function under physiological and pathophysiological conditions. This research should shed new light on the link between obesity, mitochondrial impairment, and liver dysfunction and further our understanding of the mechanisms underlying obesity-induced insulin resistance and metabolic diseases. Thus, our proposed studies should provide valuable information on the biology of DsbA-L potentially being useful as targets of anti-obesity and anti-insulin resistance therapeutics.

摘要