Genetic analysis of sphingolipid metabolism and obesity

鞘脂代谢与肥胖的遗传分析

• 批准号: 6952382
• 负责人: Greg L Harris
• 金额: $ 18.74万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6952382
• 关键词: DNA binding protein; Drosophilidae; RNA interference; arthropod genetics; bioenergetics; body weight; cholesterol; disease /disorder etiology; fatty acid biosynthesis; gene expression profiling; genetic models; genetic regulation; genetic screening; genetically modified animals; in situ hybridization; lipid metabolism; longevity; model design /development; mutant; obesity; phenotype; sphingolipids; triglycerides

DESCRIPTION (provided by applicant): The long-term objectives of the proposed research will be will be to gain insight into the involvement of sphingolipids in the etiology of obesity. These studies will use Drosophila as a model genetic organism to examine the mechanisms that underlie the development of obese characteristics when genes that regulate sphingolipid metabolism are disrupted. Six specific aims are proposed: (1) The expression profiles of genes encoding key enzymes that regulate sphingolipid metabolism will be mapped in adult flies. (2) Genetic models that systematically disrupt sphingolipid metabolism and cause obesity will be created. (3) Lipid profiles of sphingolipids, triglycerides and cholesterol will be generated in sphingolipid metabolic mutant and transgenic fly lines. (4) Obesity phenotypes of sphingolipid metabolic mutants and transgenic organisms will be characterized (5) Regulation of the fatty acid biosynthetic pathway via SREPB processing will be examined. (6) Genetic screens will be performed to identify novel genes involved in the development of obesity and modifiers of obesity phenotypes in sphingolipid metabolic mutants. It is anticipated that the proposed studies will form a firm and novel foundation for understanding the relationships between sphingolipid metabolism and obesity and may uncover novel regulatory mechanisms that govern these pathways.

描述(由申请人提供)： 这项拟议研究的长期目标将是深入了解鞘脂在肥胖病因中的作用。这些研究将以果蝇为模型遗传有机体，研究当调节鞘脂新陈代谢的基因被破坏时，肥胖特征发展的机制。提出了六个具体目标： (1)编码调节鞘脂代谢的关键酶的基因的表达谱将在成年果蝇中绘制出来。 (2)将建立系统性扰乱鞘脂代谢并导致肥胖的遗传模型。 (3)鞘脂代谢突变系和转基因果蝇系将产生鞘脂、甘油三酯和胆固醇的脂谱。 (4)神经鞘脂脂代谢突变体和转基因生物的肥胖表型特征 (5)将研究通过SREPB处理对脂肪酸生物合成途径的调节。 (6)将进行遗传筛选，以确定与肥胖发生有关的新基因和鞘磷脂代谢突变中肥胖表型的修饰者。 预计拟议的研究将为理解鞘脂代谢和肥胖之间的关系奠定坚实而新颖的基础，并可能揭示管理这些途径的新的调节机制。

项目成果

Identification of sphingolipid metabolites that induce obesity via misregulation of appetite, caloric intake and fat storage in Drosophila.

• DOI: 10.1371/journal.pgen.1003970
• 发表时间: 2013
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Walls SM Jr;Attle SJ;Brulte GB;Walls ML;Finley KD;Chatfield DA;Herr DR;Harris GL
• 通讯作者: Harris GL