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2011 Fiscal Year Final Research Report

Analysis of a novel metabolic syndrome model mouse and its molecular mechanism

Research Project

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Project/Area Number 21500386
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionUniversity of Tsukuba

Principal Investigator

ISHII Tetsuro  筑波大学, 医学医療系, 教授 (20111370)

Co-Investigator(Kenkyū-buntansha) WARABI Eiji  筑波大学, 医学医療系, 講師 (70396612)
Project Period (FY) 2009 – 2011
Keywords疾患モデル / sequestosome1 / レプチン / 肥満 / 視床下部 / 過食
Research Abstract

A mutant mouse defective in sequestosome1 gene causes mature-onset obesity. A previous study suggested importance of sequestosome1 (SQSTM1/p62) in regulation of adipocyte differentiation as a cause of obesity formation. However, our studies show overeating is the cause of the obesity formation. We constructed brain-specific SQSTM1 knock-down mouse. We found the conditional knock-down mouse exhibited similar body weight increase as the whole body gene knock-out mouse. We showed SQSTM1 is highly expressed in neurons of hypothalamus, suggesting a possibility that SQSTM1 is involved in the intracellular signaling of anorexic hormone leptin. Interesting finding is a female hormone estradiol compensates the lack of SQSTM1 in body weight control. It inhibits obesity formation through suppression of overeating of the mutant mice.

  • Research Products

    (12 results)

All 2011 2010 2009

All Journal Article (5 results) Presentation (7 results)

  • [Journal Article] Cochlear protection from acoustic injury by inhibitors of p38 MAP kinase and sequestosome 1 stress protein2010

    • Author(s)
      Tabuchi K, Oikawa K, Hoshino T, Nishimura B, Hayashi K, Yanagawa T, WarabiE, Ishii T, Tanaka S, Hara A
    • Journal Title

      Neuroscience

      Volume: 166 Pages: 665-670

  • [Journal Article] Enhanced neointimal hyperplasia and carotid artery remodeling in sequestosome 1 deficient mice2010

    • Author(s)
      Sugimoto R, Warabi E, Katayanagi S, Sakai S, Uwayama J, Yanagawa T, WatanabeA, Harada H, Kitamura K, Noguchi N, YoshidaH, Siow RCM, Mann GE, Ishii T
    • Journal Title

      J Cell Mol Med

      Volume: 14(6B) Pages: 1546-1554

  • [Journal Article] Listeria monocytogenes ActA-mediated escape from autophagic recognition2009

    • Author(s)
      Yoshikawa Y, Ogawa M, Hain T, YoshidaM, FukumatsuM, Kim M, Mimuro H, NakagawaI, Yanagawa T, Ishii T, Kakizuka A, SztulE, Chakraborty T, Sasakawa C
    • Journal Title

      Nature Cell Biol

      Volume: 11 Pages: 1233-1240

  • [Journal Article] A role of NBR1 in autophagosomal degradation of ubiquitinated substrates2009

    • Author(s)
      Kirkin V., Lamark T., Sou Y-S, BjorkoyG., Nunn J. L., Bruun J-A., Shvets E., McEwan D. G., Clausen T. H., Wild P., Bilusic I., Theurillat J-P., Overvatn A., Ishii T., Elazar Z., Komatsu M., Dikic I., Johansen T
    • Journal Title

      Molecular Cell

      Volume: 33 Pages: 1-12

  • [Journal Article] The α-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice2009

    • Author(s)
      Okada K., Yanagawa T., Warabi E., Yamatsu K., Uwayama J., Takeda K., Utsunomiya H., Yoshida H., Shoda J., Ishii T
    • Journal Title

      Hapatology Research

      Volume: 39 Pages: 490-500

  • [Presentation] Non-dipper-like hypertension in sequestosome1/p62/A170 deficient mice inearly phase of obesity2011

    • Author(s)
      Eiji Warabi, 他
    • Organizer
      英国生理学会
    • Place of Presentation
      英国Oxford市、Oxford大学
    • Year and Date
      2011-07-13
  • [Presentation] Deficiency of sequestosome1/p62/A170 inmice is associated with metabolic syndrome : (III) Non-dipper typehypertension2010

    • Author(s)
      Warabi E, 他
    • Organizer
      Internal symposium on the pathophysiology of reactive oxygen and nitrogen species
    • Place of Presentation
      スペインサラマンカ市、サラマンカ大学
    • Year and Date
      2010-05-21
  • [Presentation] Deficiency of sequestosome1/p62/A170 inmice is associated with metabolicsyndrome2010

    • Author(s)
      Ishii T, 他
    • Organizer
      (II) Enhanced neointimal hyperplasia and carotid artery remodeling in sequestosome 1 deficientmice
    • Place of Presentation
      スペインサラマンカ市、サラマンカ大学
    • Year and Date
      2010-05-21
  • [Presentation] Deficiency of sequestosome1/p62/A170 in mice is associated with metabolic syndrome (I) Obesity formation by hyperphagia2010

    • Author(s)
      Harada H, 他
    • Organizer
      Internal symposium on the pathophysiology of reactive oxygen and nitrogen species
    • Place of Presentation
      スペインサラマンカ市、サラマンカ大学
    • Year and Date
      2010-05-21
  • [Presentation] A novel mechanism of leptin re2009

    • Author(s)
      Harada Harumi, 他
    • Organizer
      The 4^<th> international congress on stress responses in biology and medicine
    • Place of Presentation
      札幌市、ガトーキングダム札幌ホテル
    • Year and Date
      2009-10-08
  • [Presentation] レプチンによる摂食調節機構におけるSQSTM1の機能2009

    • Author(s)
      原田春美, 他
    • Organizer
      アディポサイエンス研究会シンポジウム
    • Place of Presentation
      大阪府、千里阪急ホテル
    • Year and Date
      2009-08-22
  • [Presentation] Sequestosome1欠損マウスにおけるメタボリックシンドローム発症メカニズム2009

    • Author(s)
      蕨栄治, 他
    • Organizer
      れどっくす生命科学第170委員会第22回研究会
    • Place of Presentation
      大阪府、千里ライフサイエンスセンター
    • Year and Date
      2009-03-19

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Published: 2013-07-31  

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