論文

査読有り 国際誌
2020年8月18日

Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy.

Nature communications
  • Tadashi Yamamuro
  • Tsuyoshi Kawabata
  • Atsunori Fukuhara
  • Shotaro Saita
  • Shuhei Nakamura
  • Hikari Takeshita
  • Mari Fujiwara
  • Yusuke Enokidani
  • Gota Yoshida
  • Keisuke Tabata
  • Maho Hamasaki
  • Akiko Kuma
  • Koichi Yamamoto
  • Iichiro Shimomura
  • Tamotsu Yoshimori
  • 全て表示

11
1
開始ページ
4150
終了ページ
4150
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-020-17985-w

The systemic decline in autophagic activity with age impairs homeostasis in several tissues, leading to age-related diseases. A mechanistic understanding of adipocyte dysfunction with age could help to prevent age-related metabolic disorders, but the role of autophagy in aged adipocytes remains unclear. Here we show that, in contrast to other tissues, aged adipocytes upregulate autophagy due to a decline in the levels of Rubicon, a negative regulator of autophagy. Rubicon knockout in adipocytes causes fat atrophy and hepatic lipid accumulation due to reductions in the expression of adipogenic genes, which can be recovered by activation of PPARγ. SRC-1 and TIF2, coactivators of PPARγ, are degraded by autophagy in a manner that depends on their binding to GABARAP family proteins, and are significantly downregulated in Rubicon-ablated or aged adipocytes. Hence, we propose that age-dependent decline in adipose Rubicon exacerbates metabolic disorders by promoting excess autophagic degradation of SRC-1 and TIF2.

リンク情報
DOI
https://doi.org/10.1038/s41467-020-17985-w
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32811819
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434891
ID情報
  • DOI : 10.1038/s41467-020-17985-w
  • PubMed ID : 32811819
  • PubMed Central 記事ID : PMC7434891

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