Ostreolysin induces browning of adipocytes and ameliorates hepatic steatosis

Background and Aim Non‐alcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Deposition of excess triglycerides in liver cells, a hallmark of NAFLD, is associated with loss of insulin sensitivity. Ostreolysin (Oly) is a 15‐kDa fungal protein known to intera...

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Published in:	Journal of gastroenterology and hepatology Vol. 33; no. 12; pp. 1990 - 2000
Main Authors:	Nimri, Lili, Staikin, Katerina, Peri, Irena, Yehuda‐Shnaidman, Einav, Schwartz, Betty
Format:	Journal Article
Language:	English
Published:	Australia Wiley Subscription Services, Inc 01-12-2018
Subjects:	3T3-L1 Cells Adenosine kinase Adipocytes Adipocytes, Brown - drug effects Adipocytes, Brown - metabolism Adipocytes, Brown - pathology Adipocytes, White - drug effects Adipocytes, White - metabolism Adipocytes, White - pathology Adiposity - drug effects AMP AMP-Activated Protein Kinases - metabolism Animals Blood Glucose - drug effects Blood Glucose - metabolism browning Cholesterol Diet, High-Fat Disease Models, Animal Enzyme Activation Fatty liver Fungal Proteins - pharmacology Glucose tolerance Hemolysin Proteins - pharmacology Hepatocytes High fat diet I-kappa B Kinase - metabolism inflammation Insulin Kinases Liver Liver - drug effects Liver - metabolism Liver - pathology Liver diseases Male Metabolic syndrome Metabolism Mice Mice, Inbred C57BL Mimicry Non-alcoholic Fatty Liver Disease - metabolism Non-alcoholic Fatty Liver Disease - pathology Non-alcoholic Fatty Liver Disease - prevention & control non‐alcoholic fatty liver disease ostreolysin Phenotype Phenotypes Protein kinase Protein-Serine-Threonine Kinases - metabolism Signal Transduction - drug effects Steatosis Triglycerides Tumor necrosis factor-α browning non-alcoholic fatty liver disease inflammation steatosis ostreolysin
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Summary:	Background and Aim Non‐alcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Deposition of excess triglycerides in liver cells, a hallmark of NAFLD, is associated with loss of insulin sensitivity. Ostreolysin (Oly) is a 15‐kDa fungal protein known to interact with cholesterol‐enriched raft‐like membrane domains. We aim to test whether a recombinant version of Oly (rOly) can induce functional changes in vitro in adipocytes or in vivo in mice fed a high‐fat diet (HFD). Methods White preadipocyte 3T3‐L1 cells or mouse primary adipocytes treated with rOly. Male C57BL/6 mice were fed a control or HFD and treated with saline or with rOly (1 mg/kg BW) every other day for 4 weeks. Results White preadipocyte 3T3‐L1 cells or mouse primary adipocytes treated with rOly acquire a browning phenotype through activation of 5′ adenosine monophosphate‐activated protein kinase and downregulation of tumor necrosis factor α‐mediated activation of IκB kinase ε and TANK‐binding kinase 1. HFD‐fed mice treated with rOly showed a 10% reduction in BW and improved glucose tolerance, which paralleled improved expression of liver and adipose functionality, metabolism, and inflammation status, mimicking the in vitro findings. Conclusion This study provides first evidence of rOly's prevention of HFD‐induced NAFLD by stimulating liver and adipose muscle tissue functionality and oxidative potential, improving glucose tolerance, and ameliorating the metabolic profile of diet‐induced obese mice.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0815-9319 1440-1746
DOI:	10.1111/jgh.14259