Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice
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- Yuhei Mizunoe
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Yuka Sudo
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Naoyuki Okita
- Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, Chiba, Japan
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- Hidenori Hiraoka
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Kentaro Mikami
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Tomohiro Narahara
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Arisa Negishi
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Miki Yoshida
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Rikako Higashibata
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Shukoh Watanabe
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Hiroki Kaneko
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Daiki Natori
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Takuma Furuichi
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Hiromine Yasukawa
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Masaki Kobayashi
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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- Yoshikazu Higami
- Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
書誌事項
- 公開日
- 2017-02-17
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by-nc/3.0/
- DOI
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- 10.1080/15548627.2016.1274850
- 公開者
- Informa UK Limited
この論文をさがす
説明
Whether obesity accelerates or suppresses autophagy in adipose tissue is still debatable. To clarify dysregulation of autophagy and its role in pathologies of obese adipose tissue, we focused on lysosomal function, protease maturation and activity, both in vivo and in vitro. First, we showed that autophagosome formation was accelerated, but autophagic clearance was impaired in obese adipose tissue. We also found protein and activity levels of CTSL (cathepsin L) were suppressed in obese adipose tissue, while the activity of CTSB (cathepsin B) was significantly enhanced. Moreover, cellular senescence and inflammasomes were activated in obese adipose tissue. In 3T3L1 adipocytes, downregulation of CTSL deteriorated autophagic clearance, upregulated expression of CTSB, promoted cellular senescence and activated inflammasomes. Upregulation of CTSB promoted additional activation of inflammasomes. Therefore, we suggest lysosomal dysfunction observed in obese adipose tissue leads to lower autophagic clearance, resulting in autophagosome accumulation. Simultaneously, lysosomal abnormalities, including deteriorated CTSL function and compensatory activation of CTSB, caused cellular senescence and inflammasome activation. Our findings strongly suggest lysosomal dysfunction is involved in early pathologies of obese adipose tissue.
収録刊行物
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- Autophagy
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Autophagy 13 (4), 642-653, 2017-02-17
Informa UK Limited
