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:10632187
- 负责人:
- 金额:$ 2.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-12 至 2024-11-30
- 项目状态:已结题
- 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
脂肪氧化代谢对人类健康至关重要。脂肪细胞线粒体缺陷与
脂肪细胞功能障碍和胰岛素抵抗,而生活方式干预和药物治疗
促进脂肪细胞氧化能力,促进代谢健康和胰岛素敏感性。研究结束
几年来已经确定了脂肪细胞氧化代谢的重要调节因子,如成员
PGC-1共激活因子家族和PPAR(过氧化体增殖物激活的)核受体
受体)和ERR(雌激素相关受体)亚家族。这些转录因子发挥它们的作用
通过对数百个基因的直接和间接调节来影响基因表达和细胞功能
协调推进线粒体生物发生和氧化代谢。挖掘受以下因素调控的基因
PGC-1和ERRS,结合生物信息学方法确定PGC-1/ERR的关联
具有PPAR途径和新陈代谢的靶点,使我们发现了一种新的、特征不佳的
蛋白质,Mcrip2,与脂肪细胞氧化代谢高度相关。这项建议的前提是
Mcrip2是一种细胞和分子功能未知的蛋白质,目前还没有与
代谢或生理,是由PGC-1,PPAR和ERR因子诱导的,作用于增强基础和
肾上腺素刺激氧化代谢基因的表达,因此是
控制脂肪细胞氧化代谢的调控网络。Mcrip2与蛋白质的相互作用
参与mRNA的加工和转换提示Mcrip2通过调控基因发挥作用
转录后水平的表达。值得注意的是,我们对控制后遗症的机制知之甚少。
脂肪细胞氧化代谢途径中的转录步骤。拟议的工作将定义角色
Mcrip2在脂肪细胞基础氧化代谢和肾上腺素能反应中的表达
在原代棕色和腹股沟脂肪细胞中的功能途径,并描绘了Mcrip2的水平
影响基因表达。它还将确定mcrip2对线粒体的生理学意义。
功能和适应性产热,使用小鼠模型。最后,这些研究将阐明
通过定义Mcrip2蛋白结构域来影响脂肪细胞生物学的机制
基础脂肪细胞和肾上腺刺激脂肪细胞的功能和关键的Mcrip2相互作用伙伴。在……里面
总之,这项工作将首次深入了解脂肪细胞氧化功能的转录后调控,
并可能为疾病的治疗干预提出新的目标和途径,这些疾病可以从
氧化能力增强,如肥胖和肥胖相关疾病。
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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 项目类别:
Research Grant
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:
$ 2.48万 - 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:
$ 2.48万 - 项目类别:
Operating Grants
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:
$ 2.48万 - 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:
$ 2.48万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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:
$ 2.48万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Adipose Tissue T Cell Polarization and Metabolic Health in Persons Living with HIV
HIV 感染者的脂肪组织 T 细胞极化和代谢健康
- 批准号:
10619176 - 财政年份:2023
- 资助金额:
$ 2.48万 - 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:
$ 2.48万 - 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:
$ 2.48万 - 项目类别: