Adipose Tissue Macrophage Control of Metabolic Dysfunction in Diabetes
脂肪组织巨噬细胞对糖尿病代谢功能障碍的控制
基本信息
- 批准号:9400748
- 负责人:
- 金额:$ 58.11万
- 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:2017-07-18 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipocytesAdipose tissueAgeApoptosisBariatricsBiological AssayBiological MarkersBiologyCCL18 geneCSF1 geneCellsCellular biologyClinicalClinical ResearchCoculture TechniquesCollaborationsCollagenCommunicationDataDiabetes MellitusEnvironmentFunctional disorderGenesGenetic TranscriptionGlucocorticoidsGoalsHealthHumanHyperplasiaHypertrophyIL4 geneImmuneIn SituInflammationInflammatoryInflammatory ResponseInsulin ResistanceInterleukin-4KnowledgeLeadLinkMeasuresMediatingMediator of activation proteinMetabolicMetabolic ControlMetabolic DiseasesMetabolismModelingMusNon obeseNon-Insulin-Dependent Diabetes MellitusNutrientObese MiceObesityPathogenesisPathway interactionsPatientsPhenotypePhysiciansPhysiologicalPlant RootsPopulationProcessProliferatingRegulationResearchRiskRisk FactorsRodent ModelRoleScienceScientistStimulusStromal CellsSupporting CellSurgeonSystemTherapeutic InterventionThinnessTissue SampleVisceralXenograft Modeladipocyte biologyage relatedbariatric surgerybasechemokinecohortdiabetes riskdiabeticdisorder riskfunctional gaingain of functionin vivoinnovationinterestlipid biosynthesismacrophagemouse modelnon-diabeticnovelnovel markerpatient populationpatient stratificationpre-clinicalpredictive markerreceptorresponsesextargeted treatmentthree-dimensional modelingtissue biomarkers
项目摘要
PROJECT SUMMARY
Obesity-induced inflammation is a well-established mechanistic link between obesity and diabetes. Adipose
tissue macrophages (ATMs) lie at the center of the adipose tissue immune network. Many knowledge gaps
exist regarding ATM biology and its relationship to human metabolic disease. The mechanisms of ATM
accumulation, how their activation state relates to type 2 diabetes mellitus (DM), and how they communicate
with preadipocytes and adipocytes to regulate nutrient storage are incompletely understood. The goal of this
proposal is to address these knowledge gaps using complementary studies in human adipose tissue samples
and mouse models. The scientific premise for the hypotheses in this project is rooted in the observation from
our groups that visceral adipose tissue from obese (DM) subjects have higher CD206+ ATMs, fewer
preadipocytes, larger adipocytes, and manifest adipocyte metabolic dysfunction compared to obese non-DM
subjects. We propose a model whereby the expansion of CD206+ ATMs by in situ proliferation blocks
preadipocyte proliferation and differentiation to generate a dysfunctional adipose tissue environment. We will
evaluate CSF1 as a putative activator of CD206+ ATMs in humans and evaluate the function of CCL18 as a
CD206+ ATM secreted chemokine that mediates ATM-preadipocyte communication. If completed our proposal
will significantly advance our understanding of how human metabolic inflammation develops independent of
obesity and lead to substantial revisions in the current models of ATM function.
To evaluate our model, we propose to complete three specific aims: 1) To define mechanisms of CD206+
hATM proliferation and its relationship to adipocyte hypertrophy and DM status. 2) To identify mechanisms
underlying CD206+ ATM-preadipocyte crosstalk and resultant preadipocyte and adipocyte metabolic
dysfunction. 3) To evaluate the role of ATM-derived CCL18 in the regulation of adipose tissue inflammation
and metabolism. The experimental approach for all aims utilize tissue samples from a large bariatric surgery
cohort with diversity in age and sex, and assays of inflammatory and metabolic function. This study will
accomplish its goals using a team science approach between surgeons and basic scientists to close the gap
between our understanding of metainflammation in human and murine models. If completed our study can
impact health by identifying new biomarkers for DM risk independent of obesity and new pathways for
therapeutic interventions.
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)
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Carey N Lumeng其他文献
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{{ truncateString('Carey N Lumeng', 18)}}的其他基金
Depot-specific regulation of metabolism by adipose tissue stromal cell subpopulations
脂肪组织基质细胞亚群对代谢的特异性调节
- 批准号:
10685079 - 财政年份:2022
- 资助金额:
$ 58.11万 - 项目类别:
The Impact of Postnatal Overnutrition on the Adipose Tissue Immune System and Metabolic Inflammation
产后营养过剩对脂肪组织免疫系统和代谢炎症的影响
- 批准号:
9023650 - 财政年份:2015
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation by Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
8021103 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
9113707 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation by Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
8409818 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
10579916 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation by Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
8212056 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
9234511 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
10229169 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
- 批准号:
10391528 - 财政年份:2011
- 资助金额:
$ 58.11万 - 项目类别:
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支链氨基酸代谢紊乱调控“Adipocytes - Macrophages Crosstalk”诱发2型糖尿病脂肪组织功能和结构障碍的作用及机制
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