Molecular Genetics of Lipid Metabolism

脂质代谢的分子遗传学

• 批准号: 8332621
• 负责人: AMNON SCHLEGEL
• 金额: $ 32.52万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8332621
• 关键词: Active Biological Transport; Address; Adipose tissue; Adult; Animal Model; Animals; Bacterial Infections; Biochemical; Biological; Biological Models; Caring; Chronic; Cloning; Complex; Data; Defect; Developmental Biology; Discipline of obstetrics; Disease; Disease Management; Drug Delivery Systems; Dyslipidemias; Economic Factors; Economics; Embryo; Energy Metabolism; Event; Fatty Liver; Fatty acid glycerol esters; Feasibility Studies; Fertilization; Funding Opportunities; Generations; Genes; Genetic; Genetic Screening; Health; Homeostasis; Human; Hyperlipidemia; Hypertension; Image; In Situ; Individual; Intervention; Knowledge; Larva; Lead; Lipids; Lipodystrophy; Liver; Liver diseases; Metabolic; Methods; Microscopic; Molecular; Molecular Genetics; Monitor; Morbidity - disease rate; Mutagenesis; Mutate; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Obesity; Organ; Organism; Pathway interactions; Peripheral Nervous System; Persons; Phenotype; Physiological; Population; Prevalence; Proteins; Quality of life; Research; Research Infrastructure; Sanitation; Staging; Staining method; Stains; Study models; System; Techniques; Therapeutic; Tissues; Vaccination; Virus Diseases; Work; Zebrafish; combat; driving force; drug development; exhaust; feeding; gastrointestinal system; gene function; global health; insight; lipid metabolism; loss of function; mortality; mutant; non-alcoholic fatty liver; novel; obesity risk; obesity treatment; pandemic disease; positional cloning; research study; social; therapeutic target

DESCRIPTION (provided by applicant): Obesity has emerged as a world-wide health problem over the past several decades. Its complications are costly on individual and societal levels. There is urgent need to identify new drug targets for ameliorating the metabolic consequences of obesity such as type 2 diabetes mellitus, hyperlipidemia, and non-alcoholic fatty liver disease. One central aspect of obesity and its attendant illnesses that requires greater understanding is how the organism can safely store the excess lipids that accumulate throughout the body in this condition. Work over the past decade has revealed that the adipose tissue is a "battery of finite capacity," and that spill-over of lipid surplus into other tissues and organs contributes to diseas burden. This application seeks to address the need for new drug targets to combat obesity and its related illnesses by responding to the NIH's "Genetic Screens to Enhance Zebrafish Research (R01)" Funding Opportunity. A proposal to perform a large-scale forward genetic screen in zebrafish for lipid metabolic phenotypes, with a focus on hepatic steatosis (excess lipids in the liver) and altered adipose mass, is presented. We provide preliminary data underscoring both the feasibility of studying lipid metabolism in this model organism, and for identifying and characterizing completely novel and potentially druggable nodes of energy metabolism. We demonstrate that a wide-range of methods including molecular genetic, whole-animal physiologic, nutritional, biochemical, electrophysiologic, and microscopic techniques can be successfully applied to the study of mutants we intend to isolate in this screen in the hopes of arriving at a comprehensive view of how mutation of a single gene can give rise to complex metabolic phenotypes. PUBLIC HEALTH RELEVANCE: Obesity is a disease that has emerged over the past several generations in nearly all human populations, and is associated with a host of health problems. A greater understanding of how lipids are stored both in adipose tissue and elsewhere in the both may lead to new interventions to treat obesity and its related illnesses. We study how fat accumulates both in adipose tissue and elsewhere in the body by identifying and characterizing zebrafish mutants with altered lipid stores. The novel genes and pathways we identify should help address the pressing need for new treatments for obesity and its attendant illnesses.

描述（由申请人提供）：在过去的几十年里，肥胖已经成为一个全球性的健康问题。它的并发症在个人和社会层面上都是昂贵的。迫切需要确定新的药物靶点来改善肥胖的代谢后果，如2型糖尿病、高脂血症和非酒精性脂肪性肝病。