Mechanisms of fat regulation by conserved anti-obesity genes
保守抗肥胖基因的脂肪调节机制
基本信息
- 批准号:9235043
- 负责人:
- 金额:$ 36.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-02-01 至 2022-01-31
- 项目状态:已结题
- 来源:
- 关键词:AdipocytesAdipose tissueAdultAffectAllelesAlpha CellAmericanBehavioralBindingBiochemistryBiological ModelsBody WeightBody fatCandidate Disease GeneCatabolismCellsCuesCultured CellsDataData AnalysesDefectDepositionDevelopmentDiseaseDrosophila genusDrug TargetingFamilyFamily memberFat BodyFatty acid glycerol estersFutureGene ExpressionGene TargetingGenesGeneticGenetic Predisposition to DiseaseGenetic TranscriptionGenetic studyGoalsHealthHumanIndividualInheritedLarvaLipidsLiverMammalian CellMammalsMeasuresMetabolicMetabolic DiseasesMetabolismMissionModelingMolecularMolecular BiologyMusNatureObesityOrthologous GeneOutcome StudyOutputPathway interactionsPlayPredispositionProtein FamilyProteinsRNA BindingRNA Recognition MotifRNA-Binding ProteinsRecruitment ActivityRegulationRegulator GenesRegulatory PathwayResearchRoleSignal TransductionSpecificitySusceptibility GeneSystemTechniquesTestingTissuesTranscription Repressor/CorepressorTranscriptional RegulationTranslatingUnited States National Institutes of HealthVariantdrug developmentenergy balanceexperimental studyflygene functiongenome-wide analysisinnovationinsightmetabolic phenotypemutantnovelobesity treatmentoverexpressionparalogous genepreventsuccesstooluptake
项目摘要
Obesity affects a majority of American adults, with diverse and significant detrimental effects on human health.
Despite a major role for genetic background in obesity, only a small number of the human genes that
predispose individuals to obesity have been identified. Understanding the pathways that control storage of
body fat will be crucial for pinpointing genes likely to cause susceptibility to this disease. The long-term goal is
to identify genes whose activities can be modified to prevent or treat human obesity. The goals of this
application are to elucidate the mechanism by which the related RNA-binding proteins Spen and Nito regulate
adiposity, and to identify other candidates for cell-autonomous regulation of adiposity. A fruit fly model has
been developed to dissect the tissue specificity of gene function in the regulation of body fat levels, as well as
new tools to parse out the contributions of behavioral alterations and to directly measure rates of fat
incorporation into stores. A complementary approach using cultured cells will directly translate findings in the
fly model to functions in mammalian fat storage. The central hypothesis is that genes acting autonomously in
the fruit fly fat-storage tissue (the fat body, FB) to control levels of body fat will play conserved roles in
mammalian fat storage. This idea is supported by the applicant's previous success in identifying such genes,
and by preliminary data analyzing specific candidate genes, like Spen. The rationale for this project is that
regulatory pathways in fat storage tissues must respond to organismal cues to control levels of stored fat, and
that identifying key genes acting in these pathways may translate directly to insights into genetic
predispositions to human obesity. This model will be tested by pursuing three specific aims: (1) Test the
hypothesis that Spen and Nito function in an opposing manner to regulate body fat. (2) Test the hypothesis that
Spen/Nito regulate energy balance by binding specific RNAs to alter gene expression; and (3) Identify
candidate genes for novel, conserved autonomous regulators of fat storage. In Aim 1, we will determine the
mechanistic basis of defects leading to altered fat in fly larvae lacking Spen and/or Nito, two RNA-binding
proteins in the same family known to modulate transcriptional output of other pathways but never before
implicated in the control of adiposity. In Aim 2, we test a model that Spen and Nito bind specific RNAs to target
specific metabolic target genes for transcriptional control. In the Aim 3, the mouse orthologs of fly genes that
directly regulate fat storage in the FB (including Shep, Rala and NFAT) will be analyzed functionally in cultured
mouse adipocytes to identify those that also control mammalian fat storage in an autonomous manner. This
innovative combination of approaches will uncover new roles for genes whose functions in fat regulation are
currently unknown. The significance of this proposal lies in its potential to elucidate a new pathway controlling
fat storage via RNA-binding proteins, and to characterize other candidate obesity genes, providing significant
insights into the multigenic nature of this disease, and identifying new targets for future treatments.
肥胖影响着大多数美国成年人,对人体健康有各种各样的、严重的有害影响。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Tania Reis其他文献
Tania Reis的其他文献
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{{ truncateString('Tania Reis', 18)}}的其他基金
Food for thought: a virus-like signal for the energetic demands of higher cognitive functions
深思:一种类似病毒的信号,满足更高认知功能的能量需求
- 批准号:
10702143 - 财政年份:2023
- 资助金额:
$ 36.04万 - 项目类别:
Mechanisms of fat regulation by conserved anti-obesity genes
保守抗肥胖基因的脂肪调节机制
- 批准号:
10505971 - 财政年份:2021
- 资助金额:
$ 36.04万 - 项目类别:
Mechanisms of fat regulation by conserved anti-obesity genes
保守抗肥胖基因的脂肪调节机制
- 批准号:
10087917 - 财政年份:2017
- 资助金额:
$ 36.04万 - 项目类别:
Obesity and regulation of energy homeostasis in Drosophila melanogaster
果蝇的肥胖与能量稳态调节
- 批准号:
7220394 - 财政年份:2007
- 资助金额:
$ 36.04万 - 项目类别:
Obesity and regulation of energy homeostasis in Drosophila melanogaster
果蝇的肥胖与能量稳态调节
- 批准号:
7362382 - 财政年份:2007
- 资助金额:
$ 36.04万 - 项目类别:
Obesity and regulation of energy homeostasis in Drosophila melanogaster
果蝇的肥胖与能量稳态调节
- 批准号:
7569986 - 财政年份:2007
- 资助金额:
$ 36.04万 - 项目类别:
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