title: Hepatic STAMP2 alleviates high fat diet-induced hepatic steatosis and insulin resistance.
abstract: OBJECTIVE
  Most studies on the role of STAMP2 in metabolism have used adipose tissue. Little knowledge exists concerning the role of STAMP2 in the liver, which is a metabolically central target. We hypothesized that STAMP2 is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis.
  
  
  METHODS
  We examined our hypothesis using human NAFLD patient pathology samples and a high-fat diet (HFD)-induced NAFLD mouse model. The molecular mechanism underlying hepatic STAMP2-mediated lipid imbalance was explored using an oleic acid (OA)-induced NAFLD in vitro model.
  
  
  RESULTS
  Noticeably, the expression level of STAMP2 protein was reduced in the livers obtained from NAFLD patients and HFD-induced NAFLD mice. In vivo knockdown of hepatic STAMP2 by siRNA accelerated hepatic steatosis and insulin resistance in mice fed a HFD. Conversely, the delivery of adenoviral STAMP2 (Ad-STAMP2) improved hepatic steatosis in HFD-induced NAFLD mice. The expression of lipogenic or adipogenic factors was increased in both in vitro and in vivo NAFLD models but was reversed by Ad-STAMP2. Adenoviral overexpression of STAMP2 improved insulin resistance in the HFD-induced NAFLD mice. In vivo and in vitro assays demonstrated that STAMP2 modulates insulin sensitivity and glucose metabolism and that STAMP2 counteracts OA-induced insulin resistance by modulating insulin receptor substrate-1 stability.
  
  
  CONCLUSIONS
  The present study revealed that hepatic STAMP2 plays a pivotal role in preventing HFD-induced NAFLD and that STAMP2 overexpression improves hepatic steatosis and insulin resistance in NAFLD. Our findings indicate that STAMP2 may represent a suitable target for interventions targeting NAFLD.
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Hye Y
authors: HY
authors: Kim
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: So Y
authors: SY
authors: Park
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Mi H
authors: MH
authors: Lee
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Jee H
authors: JH
authors: Rho
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Yoo J
authors: YJ
authors: Oh
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Hye U
authors: HU
authors: Jung
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Seung H
authors: SH
authors: Yoo
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Na Y
authors: NY
authors: Jeong
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea.
authors: Hye J
authors: HJ
authors: Lee
authors: Department of Endocrinology, Dong-A University College of Medicine, Busan 602-714, South Korea.
authors: SungHwan
authors: S
authors: Suh
authors: Department of Microbiology, Dong-A University College of Medicine, Busan 602-714, South Korea.
authors: Su Y
authors: SY
authors: Seo
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, South Korea.
authors: JaeHun
authors: J
authors: Cheong
authors: Department of Pathology, Dong-A University College of Medicine, Busan 602-714, South Korea.
authors: Jin S
authors: JS
authors: Jeong
authors: Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea. Electronic address: yhyoo@dau.ac.kr.
authors: Young H
authors: YH
authors: Yoo
mesh_terms: D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008565:Membrane Proteins; C436323:Tiarp protein, mouse; D012313:RNA
keywords: Hepatic steatosis; Insulin resistance; NAFLD; STAMP2