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A next-generation mass spectrometric/computational strategy for aging biomarker discovery

Research Project

Project/Area Number 18H02425
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Wu Yibo  国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (50811618)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
KeywordsProteomics / White adipose tissue / Obesity / Ligand-receptor pairs / Lipid metabolism / Adipose tissue cells / Autocrine / proteomics / obesity / immune cells / adipocytes / inflammation / Adipose tissue / FACS-sorted cells / Inflammation / adipose immune cells / aging / mitochondrial function
Outline of Final Research Achievements

In this KAKENHI project, we proposed to discover biomarkers of aging and age-related metabolic diseases. We have applied the data-independent acquisition mass spectrometry (DIA-MS) method to mouse white adipose tissue (WAT) samples. We have generated a complete protein quantification map for 4727 proteins from 180 WAT samples of 53 mouse strains from the BXD aging colony. From these data, we have identified potential biomarkers for age-related obesity and metabolic dysfunction. We also expanded proteomics analysis to specific cell types from WAT tissues under high-fat and control diet. We found proteins that were significantly regulated by diet in a time-dependent manner, and candidate genes that could regulate lipid metabolism in macrophages. We have also identified cellular ligand-receptor pairs that changed significantly during diet-induced obesity. We believe our results provide novel evidence of the underlying mechanism of obesity through adipose tissue cell-cell communication.

Academic Significance and Societal Importance of the Research Achievements

We have generated a comprehensive dataset that could be informative for those who study adipose tissue function and metabolic disease. We found genes that were significantly regulated by high-fat diet and could regulate lipid metabolism. These genes could be potential drug targets to treat obesity.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (8 results)

All 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] UT Southwestern Medical Center/University of Tennessee(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The University of Tennessee(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity2021

    • Author(s)
      Shao Mengle、Hepler Chelsea、Zhang Qianbin、Shan Bo、Vishvanath Lavanya、Henry Gervaise H.、Zhao Shangang、An Yu A.、Wu Yibo、Strand Douglas W.、Gupta Rana K.
    • Journal Title

      Cell Stem Cell

      Volume: 28 Issue: 4 Pages: 685-701.e7

    • DOI

      10.1016/j.stem.2020.12.008

    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation.2020

    • Author(s)
      Mostafa D, Yanagiya A, Georgiadou E, Wu Y, Stylianides T, Rutter GA, Suzuki T*, Yamamoto T*
    • Journal Title

      Communications biology.

      Volume: 476 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s42003-020-01201-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Multi-omics and functional characterization to elucidate the role of alpha-synuclein in mitochondrial membrane compartment and function2021

    • Author(s)
      Yibo Wu
    • Organizer
      2021 RIKEN-Luxembourg Digital Scientific Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rewiring of Immune Cell Network in Adipose Tissue in Obesity2019

    • Author(s)
      Yibo Wu
    • Organizer
      The 3rd RIKEN IMS-Stanford ISCBRM Joint Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] PreadProfiler

    • URL

      http://preadprofiler.us-east-2.elasticbeanstalk.com/about

    • Related Report
      2020 Annual Research Report
  • [Remarks] A new set of BXD recombinant inbred lines..

    • URL

      https://bmcgenet.biomedcentral.com/articles/10.1186/1471-2156-5-7

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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