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A strategy for discovery of endocrine interactions

A strategy for discovery of endocrine interactions
发现内分泌相互作用的策略
批准号:
10347305
负责人:
Marcus Michael Seldin
金额:
$24.75万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-04-03 至 2022-11-30

项目摘要

项目成果

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中文摘要
翻译
项目总结/文摘
英文摘要
Project Summary/Abstract We developed a bioinformatics framework which uses multi-tissue expression arrays and publicly available resources to statistically rank and functionally annotate endocrine axes. By applying this method to expression profiles within the Hybrid Mouse Diversity Panel (HMDP), we identify many known and several novel inter-tissue circuits. We further show the utility of this approach by uncovering a new adipose-to-skeletal muscle endocrine axis which shows promise as a therapeutic target for metabolic syndrome in both mice and humans. Functional experiments show adipose-derived Lipocalin-5 (LCN5) is sufficient to enhance skeletal muscle mitochondrial activity and gene expression. When overexpressed in a mouse model, the secreted peptide prevents and rescues diet-induced metabolic syndrome as measured by insulin- and glucose- tolerance. We also show that the human orthologue of the protein is sufficient to enhance expression of similar oxidation and biogenesis genes in human muscle cells. We further expand this method to identify adipose-derived Inter α-trypsin inhibitor 5 (Itih5) as a conserved regulator of cardiomyocyte function. Specifically, correlative data in mice and humans and mechanistic studies show ITIH5 as a suppressor of cardiomyocyte hypertrophy. The goal of this proposal is to 1) Mechanistically dissect how Lipocalin-5/6 enhances skeletal muscle mitochondrial activity in mice and humans and 2) Utilize both global and targeted studies to understand biologic processes by which ITIH5 reduces cardiac hypertrophy in a physiologic and pathophysiologic state.
期刊论文(9)
专著(0)
科研奖励(0)
会议论文
Systems-based approaches for investigation of inter-tissue communication.
用于研究组织间通信的基于系统的方法。
DOI: 10.1194/jlr.s090316
发表时间: 2019
期刊: Journal of lipid research
影响因子: 6.5
作者: [Seldin,MarcusM, Lusis,AldonsJ]
通讯作者: Lusis,AldonsJ
DOI: 10.1161/circulationaha.120.050186
发表时间: 2021-05-04
期刊: Circulation
影响因子: 37.8
作者: [von Scheidt M, Zhao Y, de Aguiar Vallim TQ, Che N, Wierer M, Seldin MM, Franzén O, Kurt Z, Pang S, Bongiovanni D, Yamamoto M, Edwards PA, Ruusalepp A, Kovacic JC, Mann M, Björkegren JLM, Lusis AJ, Yang X, Schunkert H]
通讯作者: Schunkert H
Systems genetics applications in metabolism research.
系统遗传学在代谢研究中的应用。
DOI: 10.1038/s42255-019-0132-x
发表时间: 2019
期刊: Nature metabolism
影响因子: 20.8
作者: [Seldin,Marcus, Yang,Xia, Lusis,AldonsJ]
通讯作者: Lusis,AldonsJ
DOI: 10.1161/atvbaha.118.311266
发表时间: 2018-09
期刊: Arteriosclerosis, thrombosis, and vascular biology
影响因子: --
作者: [Erbilgin A, Seldin MM, Wu X, Mehrabian M, Zhou Z, Qi H, Dabirian KS, Sevag Packard RR, Hsieh W, Bensinger SJ, Sinha S, Lusis AJ]
通讯作者: Lusis AJ
7
    Identification of osteoclast endocrine and paracrine communications by systems genetics approaches
    Integrative approaches to dissection of endocrine communication
    • 批准号:
      10324086
    • 项目类别:
    • 资助金额:
      $61.8万
    • 财政年份:
      2021
    • 负责人:
      Marcus Michael Seldin
    • 依托单位:
    Integrative approaches to dissection of endocrine communication
    • 批准号:
      10490425
    • 项目类别:
    • 资助金额:
      $61.8万
    • 财政年份:
      2021
    • 负责人:
      Marcus Michael Seldin
    • 依托单位:
    Integrative approaches to dissection of endocrine communication
    • 批准号:
      10680567
    • 项目类别:
    • 资助金额:
      $61.8万
    • 财政年份:
      2021
    • 负责人:
      Marcus Michael Seldin
    • 依托单位:
    海外基金