Regulators of adipocyte oxidative metabolism
脂肪细胞氧化代谢的调节因子
基本信息
- 批准号:10391144
- 负责人:
- 金额:$ 45.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-01 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:AdipocytesAdipose tissueAdrenergic AgentsAdrenergic AgonistsBiogenesisBioinformaticsBiologyBody TemperatureBrown FatCardiovascular DiseasesCell RespirationCell physiologyCellsCodeCoupledDefectDevelopmentDiseaseERR1 proteinEnvironmentEstrogen Nuclear ReceptorFamilyFunctional disorderGene ExpressionGenesGenetic TranscriptionGenomeGoalsGrantHealthHeartHomeostasisHumanInsulin ResistanceInterventionKidneyLeadLinkLipidsLiverMessenger RNAMetabolicMetabolismMiningMitochondriaMitochondrial ProteinsMolecularMusMyopathyNatureNon-Insulin-Dependent Diabetes MellitusNorepinephrineNuclearNuclear Orphan ReceptorNuclear ReceptorsNutrientObesityObesity associated diseaseOrganellesOxidative PhosphorylationOxidesPathway interactionsPatternPeroxisome Proliferator-Activated ReceptorsPharmacologyPhysiologicalPhysiologyPost-Transcriptional RegulationProteinsPublishingReceptor SignalingRegulationRegulator GenesRegulatory ElementRoleSignal TransductionSkeletal MuscleSumTertiary Protein StructureTestingTherapeutic InterventionThermogenesisTissuesWorkadipocyte biologybasecell typeestrogen-related receptorgene inductioninsightinsulin sensitivitylifestyle interventionloss of functionmembermouse modelnoveloverexpressionoxidationphysiologic stressorrecruitresponsetraittranscription factor
项目摘要
PROJECT SUMMARY
Adipose oxidative metabolism is central to human health. Defects in adipocyte mitochondria are linked to
adipocyte dysfunction and insulin resistance, whereas lifestyle interventions and pharmacological agents
that promote adipocyte oxidative capacity promote metabolic health and insulin sensitivity. Studies over
several years have identified important regulators of adipocyte oxidative metabolism, such as members
of the PGC-1 coactivator family, and nuclear receptors of the PPAR (peroxisome proliferator-activated
receptor) and ERR (Estrogen-related receptor) subfamilies. These transcription factors exert their effects
on gene expression and cellular function by both direct and indirect regulation of hundreds of genes that
coordinately promote mitochondrial biogenesis and oxidative metabolism. Mining of genes regulated by
PGC-1s and ERRs, coupled to bioinformatic approaches to determine associations of PGC-1/ERR
targets with PPAR pathways and metabolism, has led us to identify a new and poorly characterized
protein, Mcrip2, as highly associated with adipocyte oxidative metabolism. The premise of this proposal
is that Mcrip2, a protein of unknown cellular and molecular function, that has not been linked yet to
metabolism or physiology, is induced by PGC-1, PPAR and ERR factors, acts to enhance basal and
adrenergically stimulated expression of oxidative metabolism genes, and is thus a critical element of the
regulatory networks that control adipocyte oxidative metabolism. Interactions of Mcrip2 with proteins
involved in mRNA processing and turnover suggest that Mcrip2 exerts its function by regulating gene
expression at the post-transcriptional level. Notably, we know little about mechanisms controlling post-
transcriptional steps in adipocyte oxidative metabolism pathways. The proposed work will define the role
of Mcrip2 in adipocyte basal oxidative metabolism and adrenergic responses, using gain- and loss-of
function approaches in primary brown and inguinal adipocytes, and delineate the level at which Mcrip2
impacts gene expression. It will also determine the physiologic significance of Mcrip2 for mitochondrial
function and adaptive thermogenesis, using a mouse model. Finally, the studies will elucidate the
mechanism by which Mcrip2 impacts adipocyte biology, by defining Mcrip2 protein domains required for
function and critical Mcrip2 interacting partners in basal and adrenergically stimulated adipocytes. In
sum, the work will give first insights into post-transcriptional regulation of adipocyte oxidative function,
and may suggest new targets and avenues for therapeutic intervention in diseases that can benefit from
increases in oxidative capacity, such as obesity and obesity-related diseases.
项目总结
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Anastasia Kralli其他文献
Anastasia Kralli的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Anastasia Kralli', 18)}}的其他基金
Estrogen-Related Receptor Pathways in Skeletal Muscle
骨骼肌中雌激素相关受体途径
- 批准号:
9319399 - 财政年份:2016
- 资助金额:
$ 45.03万 - 项目类别:
Estrogen-Related Receptor Pathways in Skeletal Muscle
骨骼肌中雌激素相关受体途径
- 批准号:
9324242 - 财政年份:2016
- 资助金额:
$ 45.03万 - 项目类别:
Estrogen-Related Receptor Pathways in Skeletal Muscle
骨骼肌中雌激素相关受体途径
- 批准号:
9029852 - 财政年份:2015
- 资助金额:
$ 45.03万 - 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
- 批准号:
8876661 - 财政年份:2012
- 资助金额:
$ 45.03万 - 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
- 批准号:
8708064 - 财政年份:2012
- 资助金额:
$ 45.03万 - 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
- 批准号:
8534114 - 财政年份:2012
- 资助金额:
$ 45.03万 - 项目类别:
The Role of Estrogen-Related Receptors in Energy Homeostasis
雌激素相关受体在能量稳态中的作用
- 批准号:
8401824 - 财政年份:2012
- 资助金额:
$ 45.03万 - 项目类别:
相似海外基金
Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
- 批准号:
MR/Y013891/1 - 财政年份:2024
- 资助金额:
$ 45.03万 - 项目类别:
Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
- 批准号:
BB/Y006542/1 - 财政年份:2024
- 资助金额:
$ 45.03万 - 项目类别:
Research Grant
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
- 批准号:
23H03323 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
- 批准号:
23K08293 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
- 批准号:
479570 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
- 批准号:
488898 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Operating Grants
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
- 批准号:
23K19922 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
A mechanism of lipid accumulation in brown adipose tissue
棕色脂肪组织中脂质积累的机制
- 批准号:
10605981 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
- 批准号:
10813753 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
- 批准号:
10604611 - 财政年份:2023
- 资助金额:
$ 45.03万 - 项目类别: