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 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.