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ID 49928
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Author
Iseda, Izumi
Higashio, Kanji
Kanzaki, Motoko
Inoue, Kentaro
Terami, Takahiro
Katayama, Akihiro
Hida, Kazuyuki
Horiguchi, Chikage Sato
Matsuki, Yasushi
Hiramatsu, Ryuji
Yagita, Hideo
Kakuta, Shigeru
Iwakura, Yoichiro
Abstract
It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 2012
Published Date
2012-11
Publication Title
Diabetes
Volume
volume61
Issue
issue11
Start Page
2823
End Page
2832
ISSN
0012-1797
Content Type
Journal Article
Official Url
http://dx.doi.org/10.2337/db12-0232
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/49735
language
英語
File Version
author
Refereed
True
DOI
Web of Sience KeyUT