Mechanisms of human adipose depot development and impact of Diabetes
人体脂肪库发育机制及糖尿病的影响
基本信息
- 批准号:10418655
- 负责人:
- 金额:$ 49.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-17 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAdipocytesAdipose tissueAffectBody fatCell Differentiation processCellsCellular Metabolic ProcessCellular StructuresCharacteristicsClone CellsDefectDerivation procedureDeteriorationDevelopmentDiabetes MellitusFatty acid glycerol estersFemaleFunctional disorderGenerationsGenesGenomicsGoalsHealthHeart DiseasesHeterogeneityHormonalHumanImpairmentIndividualInsulinLeadMesenchymal Stem CellsMetabolicMetabolic DiseasesMetabolismMethodsMultipotent Stem CellsMusNatureNon-Insulin-Dependent Diabetes MellitusNutritionalObesityOnset of illnessPathway interactionsPeripheralPersonsPhysiologicalPositioning AttributePropertyResearchResolutionRiskStem Cell DevelopmentTestingTissuesVariantWeight GainWorkadipocyte differentiationdisorder riskimpaired capacityimprovedin vivoinsightmalemouse modelnovelprogenitorresponsestem cell populationstem cellstissue repairtranscriptometranscriptomics
项目摘要
ABSTRACT
More than total adiposity, the relative distribution of adipose tissue among central and peripheral depots is
a critical determinant of Type 2 Diabetes (T2DM) and cardio metabolic disease risk. The goal of this
proposal is to use novel mesenchymal progenitor cell derivation and single-cell clone genomic sequencing
approaches to fully identify and characterize the diversity of adipocytes that compose these human depots and
their developmental mechanisms. To this end, we will leverage exciting recent methods whereby we can
generate large numbers of mesenchymal progenitor cells from human adipose tissue with minimal loss of
multipotency. These cells differentiate into adipocytes that are similar to those from the depot of origin, and
their transcriptomes reveal the existence of at least three types of “white” human adipocytes, as well as the
thermogenic “beige/brite” type. We are now in a strong position to test the hypothesis that metabolically
distinct human adipose depots, gluteal and abdominal, are composed of different adipocyte classes that
develop from specific mesenchymal progenitor cells, and to provide full transcriptomic profiles of these
adipocytes and their progenitors. Furthermore, it is known that diabetes affects multipotent progenitor cells,
leading to impaired capacity to generate healthy adipocytes and repair tissue, further deterioration of insulin
responsiveness. We will test the hypothesis that human T2DM alters mesenchymal progenitor diversity
and determine how this defect leads to abnormal adipose tissue development in vivo. Our specific aims are:
1. To test the hypothesis that the different functional properties of human adipose tissue depots are due to
intrinsic differences in their content of adipocyte subtypes derived from specific mesenchymal progenitor
cells. 2: To test the hypothesis that T2DM preferentially impairs development of specific mesenchymal
progenitor subsets and adipocytes derived from these cells, and 3: To define the physiological properties of
adipocyte subtypes through tissue generation in vivo. These studies will provide a new high-resolution view
of the cellular structure of human adipose tissue depots, of developmental mechanisms that lead to adipocyte
subtypes, and insight into developmental alterations that contribute to T2DM physiopathology.
摘要
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)
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Silvia Corvera其他文献
Silvia Corvera的其他文献
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{{ truncateString('Silvia Corvera', 18)}}的其他基金
Human adipose tissue in control of sympathetic tone and metabolic rate
人类脂肪组织控制交感神经张力和代谢率
- 批准号:
10749552 - 财政年份:2023
- 资助金额:
$ 49.41万 - 项目类别:
Mechanisms of human adipose depot development and impact of Diabetes
人体脂肪库发育机制及糖尿病的影响
- 批准号:
10019532 - 财政年份:2019
- 资助金额:
$ 49.41万 - 项目类别:
Mechanisms of human adipose depot development and impact of Diabetes
人体脂肪库发育机制及糖尿病的影响
- 批准号:
10166839 - 财政年份:2019
- 资助金额:
$ 49.41万 - 项目类别:
University of Massachusetts Center for Clinical and Translational Science
马萨诸塞大学临床与转化科学中心
- 批准号:
9127400 - 财政年份:2015
- 资助金额:
$ 49.41万 - 项目类别:
FASEB SRC on Glucose transport: Gateway for metabolic systems Biology
FASEB SRC 关于葡萄糖转运:代谢系统生物学的门户
- 批准号:
8595738 - 财政年份:2013
- 资助金额:
$ 49.41万 - 项目类别:
Medical Scientist Training at UMMS Administrative Supplement
UMMS 医学科学家培训行政补充
- 批准号:
9900318 - 财政年份:2013
- 资助金额:
$ 49.41万 - 项目类别:
Adipose Tissue Angiogenesis and Metabolic Disease
脂肪组织血管生成和代谢疾病
- 批准号:
8187450 - 财政年份:2011
- 资助金额:
$ 49.41万 - 项目类别:
Adipose Tissue Angiogenesis and Metabolic Disease
脂肪组织血管生成和代谢疾病
- 批准号:
8470640 - 财政年份:2011
- 资助金额:
$ 49.41万 - 项目类别:
Adipose Tissue Angiogenesis and Metabolic Disease
脂肪组织血管生成和代谢疾病
- 批准号:
8668046 - 财政年份:2011
- 资助金额:
$ 49.41万 - 项目类别:
FASEB SRC on Glucose Transporters, Signaling and Diabetes
关于葡萄糖转运蛋白、信号传导和糖尿病的 FASEB SRC
- 批准号:
8200163 - 财政年份:2011
- 资助金额:
$ 49.41万 - 项目类别:
相似国自然基金
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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