Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 장기석 | - |
dc.date.accessioned | 2020-01-13T05:29:59Z | - |
dc.date.available | 2020-01-13T05:29:59Z | - |
dc.date.issued | 2019-05 | - |
dc.identifier.citation | JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, v. 34, no. 12, Page. 2206-2218 | en_US |
dc.identifier.issn | 0815-9319 | - |
dc.identifier.issn | 1440-1746 | - |
dc.identifier.uri | https://onlinelibrary.wiley.com/doi/full/10.1111/jgh.14740 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/121726 | - |
dc.description.abstract | Background and Aim: Receptor-interacting serine/threonine kinase 3 and mixed lineage kinase domain-like pseudokinase (MLKL) have gained attention as apoptosis alternate cell death signaling molecules. We aimed to evaluate the role of MLKL in non-alcoholic fatty liver disease (NAFLD). Methods: Hepatic tissue MLKL expression was compared between NAFLD patients and healthy controls. High-fat diet was fed to wild-type and MLKL-knockout (KO) mice for 12 weeks. Brown adipose fat tissue was measured by [18F]-fluorodeoxyglucose positron emission tomography. Energy expenditure was measured by indirect calorimetry. Anti-MLKL effects were also evaluated in in vitro setting using U937 and HepG2 cells. Results: Hepatic tissue MLKL expression increased in NAFLD patients compared with healthy controls. MLKL expression increased according to the degree of steatosis, ballooning, and inflammation. High-fat diet-fed MLKL-KO mice displayed decreased alanine aminotransferase, triglycerides, liver weight, NAFLD activity score (6.3 vs 3.5, P < 0.001), steatosis score (3.0 vs 1.8, P < 0.001), inflammation, and ballooning degeneration compared with wild-type mice. SREBP1c, fatty acid synthase, and SCD-1 expressions decreased in MLKL-KO mice. Adipose tissue F4/80-positive crown-like structures were also reduced in MLKL-KO mice. HepG2 cells treated with necrosulfonamide (an MLKL inhibitor) showed reduced Nile red staining and reduced SREBP1c and SCD-1 expressions. Stimulation of necroptosis using lipopolysaccharide + caspase inhibitor (zVAD) increased CXCL1/2 expressions in U937 monocyte cells. Lipopolysaccharide + zVAD-induced increased expressions of CXCL1/2 were reduced with necrosulfonamide treatment. Conclusions: Mixed lineage kinase domain-like pseudokinase inhibition has protective effects in non-alcoholic steatohepatitis by decreasing hepatic de novo fat synthesis and chemokine (C-X-C motif) ligand expressions. © 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd | en_US |
dc.language.iso | en | en_US |
dc.publisher | WILEY | en_US |
dc.subject | hepatic inflammation | en_US |
dc.subject | mixed lineage kinase domain-like (MLKL) | en_US |
dc.subject | NAFLD | en_US |
dc.title | Decrease in fat de novo synthesis and chemokine ligand expression in non-alcoholic fatty liver disease caused by inhibition of mixed lineage kinase domain-like pseudokinase | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1111/jgh.14740 | - |
dc.relation.page | 1-13 | - |
dc.relation.journal | JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | - |
dc.contributor.googleauthor | Saeed, Waqar Khalid | - |
dc.contributor.googleauthor | Jun, Dae Won | - |
dc.contributor.googleauthor | Jang, Kiseok | - |
dc.contributor.googleauthor | Oh, Ju Hee | - |
dc.contributor.googleauthor | Chae, Yeon Ji | - |
dc.contributor.googleauthor | Lee, Jai Sun | - |
dc.contributor.googleauthor | Koh, Dong Hee | - |
dc.contributor.googleauthor | Kang, Hyeon Tae | - |
dc.relation.code | 2019000817 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | medartisan | - |
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