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
| Autor: | Hyeon Tae Kang, Ju Hee Oh, Dong Hee Koh, Kiseok Jang, Yeon Ji Chae, Waqar Khalid Saeed, Jai Sun Lee, Dae Won Jun |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Chemokine Adipose tissue Diet High-Fat Ligands 03 medical and health sciences Ballooning degeneration 0302 clinical medicine Adipose Tissue Brown Non-alcoholic Fatty Liver Disease Internal medicine medicine Animals Humans Protein Kinase Inhibitors Mice Knockout Acrylamides Sulfonamides Hepatology biology business.industry Fatty liver Gastroenterology Hep G2 Cells U937 Cells medicine.disease Lipids Mice Inbred C57BL CXCL1 Fatty acid synthase Endocrinology Liver Case-Control Studies 030220 oncology & carcinogenesis Necroptosis biology.protein 030211 gastroenterology & hepatology Steatosis Steatohepatitis Energy Metabolism business Chemokines CXC Protein Kinases Gene Deletion |
| Zdroj: | Journal of Gastroenterology and Hepatology. 34:2206-2218 |
| ISSN: | 1440-1746 0815-9319 |
| Popis: | 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 [18 F]-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 |
| Databáze: | OpenAIRE |
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