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Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex
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 E...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478540/ https://www.ncbi.nlm.nih.gov/pubmed/22837305 http://dx.doi.org/10.2337/db12-0232 |
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author | Nakatsuka, Atsuko Wada, Jun Iseda, Izumi Teshigawara, Sanae Higashio, Kanji Murakami, Kazutoshi Kanzaki, Motoko Inoue, Kentaro Terami, Takahiro Katayama, Akihiro Hida, Kazuyuki Eguchi, Jun Horiguchi, Chikage Sato Ogawa, Daisuke Matsuki, Yasushi Hiramatsu, Ryuji Yagita, Hideo Kakuta, Shigeru Iwakura, Yoichiro Makino, Hirofumi |
author_facet | Nakatsuka, Atsuko Wada, Jun Iseda, Izumi Teshigawara, Sanae Higashio, Kanji Murakami, Kazutoshi Kanzaki, Motoko Inoue, Kentaro Terami, Takahiro Katayama, Akihiro Hida, Kazuyuki Eguchi, Jun Horiguchi, Chikage Sato Ogawa, Daisuke Matsuki, Yasushi Hiramatsu, Ryuji Yagita, Hideo Kakuta, Shigeru Iwakura, Yoichiro Makino, Hirofumi |
author_sort | Nakatsuka, Atsuko |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3478540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-34785402013-11-01 Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex Nakatsuka, Atsuko Wada, Jun Iseda, Izumi Teshigawara, Sanae Higashio, Kanji Murakami, Kazutoshi Kanzaki, Motoko Inoue, Kentaro Terami, Takahiro Katayama, Akihiro Hida, Kazuyuki Eguchi, Jun Horiguchi, Chikage Sato Ogawa, Daisuke Matsuki, Yasushi Hiramatsu, Ryuji Yagita, Hideo Kakuta, Shigeru Iwakura, Yoichiro Makino, Hirofumi Diabetes Obesity Studies 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. American Diabetes Association 2012-11 2012-10-16 /pmc/articles/PMC3478540/ /pubmed/22837305 http://dx.doi.org/10.2337/db12-0232 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Obesity Studies Nakatsuka, Atsuko Wada, Jun Iseda, Izumi Teshigawara, Sanae Higashio, Kanji Murakami, Kazutoshi Kanzaki, Motoko Inoue, Kentaro Terami, Takahiro Katayama, Akihiro Hida, Kazuyuki Eguchi, Jun Horiguchi, Chikage Sato Ogawa, Daisuke Matsuki, Yasushi Hiramatsu, Ryuji Yagita, Hideo Kakuta, Shigeru Iwakura, Yoichiro Makino, Hirofumi Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex |
title | Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex |
title_full | Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex |
title_fullStr | Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex |
title_full_unstemmed | Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex |
title_short | Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex |
title_sort | vaspin is an adipokine ameliorating er stress in obesity as a ligand for cell-surface grp78/mtj-1 complex |
topic | Obesity Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478540/ https://www.ncbi.nlm.nih.gov/pubmed/22837305 http://dx.doi.org/10.2337/db12-0232 |
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