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Hepatic STAMP2 mediates recombinant FGF21‐induced improvement of hepatic iron overload in nonalcoholic fatty liver disease
Author(s) -
Kim Hye Young,
Kwon Woo Young,
Park Joon Beom,
Lee Mi Hwa,
Oh Yoo Jin,
Suh SungHwan,
Baek Yang Hyun,
Jeong Jin Sook,
Yoo Young Hyun
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000790r
Subject(s) - nonalcoholic fatty liver disease , fgf21 , recombinant dna , nonalcoholic steatohepatitis , fatty liver , medicine , disease , chemistry , biochemistry , receptor , gene , fibroblast growth factor
Abstract Although previous studies have shown that the administration of fibroblast growth factor 21 (FGF21) reverses hepatic steatosis, the mechanism by which FGF21 exerts a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) is not yet entirely understood. We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable target for NAFLD. We investigated the mechanism underlying the therapeutic effect of recombinant FGF21 on NAFLD, focusing on the involvement of hepatic STAMP2. In this study, we used human nonalcoholic steatosis patient pathology samples, C57BL/6 mice for a high‐fat diet (HFD)‐induced in vivo NAFLD model, and used human primary hepatocytes and HepG2 cells for oleic acid (OA)‐induced in vitro NAFLD model. We observed that recombinant FGF21 treatment ameliorated hepatic steatosis and insulin resistance through the upregulation of STAMP2 expression. We further observed hepatic iron overload (HIO) and reduced iron exporter, ferroportin expression in the liver samples obtained from human NAFLD patients, and HFD‐induced NAFLD mice and in OA‐treated HepG2 cells. Importantly, recombinant FGF21 improved HIO through the hepatic STAMP2‐mediated upregulation of ferroportin expression. Our data suggest that hepatic STAMP2 may represent a suitable therapeutic intervention target for FGF21‐induced improvement of NAFLD accompanying HIO.