title: Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex.
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.
authors: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Atsuko
authors: A
authors: Nakatsuka
authors: Jun
authors: J
authors: Wada
authors: Izumi
authors: I
authors: Iseda
authors: Sanae
authors: S
authors: Teshigawara
authors: Kanji
authors: K
authors: Higashio
authors: Kazutoshi
authors: K
authors: Murakami
authors: Motoko
authors: M
authors: Kanzaki
authors: Kentaro
authors: K
authors: Inoue
authors: Takahiro
authors: T
authors: Terami
authors: Akihiro
authors: A
authors: Katayama
authors: Kazuyuki
authors: K
authors: Hida
authors: Jun
authors: J
authors: Eguchi
authors: Chikage Sato
authors: CS
authors: Horiguchi
authors: Daisuke
authors: D
authors: Ogawa
authors: Yasushi
authors: Y
authors: Matsuki
authors: Ryuji
authors: R
authors: Hiramatsu
authors: Hideo
authors: H
authors: Yagita
authors: Shigeru
authors: S
authors: Kakuta
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Hirofumi
authors: H
authors: Makino
mesh_terms: D054392:Adipokines / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D050956:HSP40 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D015843:Serpins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D054392:Adipokines; C092319:Dnajc1 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008024:Ligands; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D015843:Serpins; C577327:vaspin protein, mouse